Acute diverticulitis: beyond the diagnosis: predictive role of CT in assessing risk of recurrence and clinical implications in non-operative management of acute diverticulitis.

PURPOSE: The aim of the study is to identify CT findings that are predictive of recurrence of acute uncomplicated colonic diverticulitis, to better risk-stratify these patients for whom guidelines recommend a conservative outpatient treatment and to determine the appropriate management with an improvement of health costs. MATERIALS AND METHODS: Over the past year, 33 patients enrolled in an outpatient integrated care pathway (PDTA) for uncomplicated acute diverticulitis with 1-year follow-up period, without recurrence, and 33 patients referred to Emergency Department for a recurrent acute diverticulitis were included. Images of admission CT were reviewed by two radiologists and the imaging features were analyzed and compared with Chi-square and Student t tests. Univariate and multivariate Cox regression models were employed to identify parameters that significantly predicted recurrence in 1-year follow-up period and establish cutoff and recurrence-free rates. The maximally selected rank statistics (MSRS) were used to identify the optimal wall thickening cutoff for the prediction of recurrence. RESULTS: Patients with recurrence showed a greater mean parietal thickness compared to the group without recurrence (16 mm vs. 11.5 mm; HR 1.25, p < 0.001) and more evidence of grade 4 of peridiverticular inflammation (40% vs. 12%, p = 0.009, HR 3.44). 12-month recurrence-free rates progressively decrease with increasing thickness and inflammation. In multivariate analysis, only parietal thickness maintained its predictive power with an optimal cutpoint > 15 mm that causes a sixfold increased risk of recurrence (HR 6.22; 95% CI, 3.05-12.67; p < 0.001). Beyond thickness and peridiverticular inflammation, predictive value of early recurrence within 90 days from the 1st episode resulted also an Hinchey Ib on admission CT. CONCLUSIONS: The maximum wall thickening and the grade of peridiverticular inflammation can be considered as predictive factors of recurrence and may be helpful in selecting patients for a tailored treatment to prevent the risk of recurrence.

Chest CT features of COVID-19 in vaccinated versus unvaccinated patients: use of CT severity score and outcome analysis.

OBJECTIVES: To evaluate the impact of vaccination on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and moreover on coronavirus disease 2019 (COVID-19) pneumonia, by assessing the extent of lung disease using the CT severity score (CTSS). METHODS: Between September 2021 and February 2022, SARS-CoV-2 positive patients who underwent chest CT were retrospectively enrolled. Anamnestic and clinical data, including vaccination status, were obtained. All CT scans were evaluated by two readers using the CTSS, based on a 25-point scale. Univariate and multivariate logistic regression analyses were performed to evaluate the associations between CTSS and clinical or demographic variables. An outcome analysis was used to differentiate clinical outcome between vaccinated and unvaccinated patients. RESULTS: Of the 1040 patients (537 males, 503 females; median age 58 years), 678 (65.2%) were vaccinated and 362 (34.8%) unvaccinated. Vaccinated patients showed significantly lower CTSS compared to unvaccinated patients (p < 0.001), also when patients without lung involvement (CTSS = 0) were excluded (p < 0.001). Older age, male gender and lower number of doses administered were associated with higher CTSS, however, in the multivariate analysis, vaccination status resulted to be the variable with the strongest association with CTSS. Clinical outcomes were significantly worse in unvaccinated patients, including higher number of ICU admissions and higher mortality rates. CONCLUSIONS: Lung involvement during COVID-19 was significantly less severe in vaccinated patients compared with unvaccinated patients, who also showed worse clinical outcomes. Vaccination status was the strongest variable associated to the severity of COVID-related, more than age, gender, and number of doses administered.

Assessment of sST2 Behaviors to Evaluate Severity/Clinical Impact of Acute Pulmonary Embolism.

Pulmonary embolism (PE) is a potentially life-threatening disorder. Beyond its usefulness in the prognostic stratification of heart failure, sST2 can represent a biomarker with high utility in several acute conditions. Our study was aimed to investigate whether sST2 can be used as a clinical marker of severity and prognostic outcome in acute PE. We enrolled 72 patients with documented PE and 38 healthy subjects; we measured the plasma concentrations of sST2 to evaluate the prognostic and severity performance of different levels of sST2 according to its association with the pulmonary embolism severity index (PESI) score and several parameters of respiratory function. PE patients had significantly higher levels of sST2 compared with healthy subjects (87.74 ± 17.1 vs. 17.1 ± 0.4 ng/mL, p < 0.001); we found higher PESI scores and serum lactate values in the group of patients with sST2 > 35 ng/mL compared with patients with sST2 < 35 ng/mL (138.7 ± 14.9 vs. 103.7 ± 15.1 and 2.43 ± 0.69 vs. 1.025 ± 0.05 mmol/L, respectively; p < 0.05). Patients with sST2 > 35 ng/mL showed higher radiological severity of PE compared with patients with sST2 < 35 ng/mL. Moreover, sST2 was the strongest parameter with a discriminative capacity for the development of acute respiratory failure and a PESI score >106 with respect to C reactive protein (CRP), creatinine, d-dimer, and serum lactate. We clearly demonstrated that sST2 significantly increased in PE and that its elevation was associated with disease severity. Therefore, sST2 may be used as a clinical marker in the evaluation of PE severity. However, further studies with larger patient populations are required to confirm these findings.

Prognostic Role of sST2 in Acute Heart Failure and COVID-19 Infection-A Narrative Review on Pathophysiology and Clinical Prospective.

The importance of cardiovascular biomarkers in clinical practice increased dramatically in the last years, and the interest extends from the diagnosis purpose to prognostic applications and response to specific treatment. Acute heart failure, ischemic heart failure, and COVID-19 infection represent different clinical settings that are challenging in terms of the proper prognostic establishment. The aim of the present review is to establish the useful role of sST2, the soluble form of the interleukin-1 receptor superfamily (ST2), physiologically involved in the signaling of interleukin-33 (IL-33)-ST2 axis, in the clinical setting of acute heart failure (HF), ischemic heart disease, and SARS-CoV-2 acute infection. Molecular mechanisms associated with the IL33/ST2 signaling pathways are discussed in view of the clinical usefulness of biomarkers to early diagnosis, evaluation therapy to response, and prediction of adverse outcomes in cardiovascular diseases.

Incidence and Determinants of Spontaneous Cardioversion of Early Onset Symptomatic Atrial Fibrillation.

Atrial fibrillation (AF) is the most frequent chronic arrhythmia worldwide, and it is associated with significant morbidity and mortality, making it a considerable burden both to patients and the healthcare system. Nowadays, an early attempt to restore sinus rhythm in acute symptomatic AF through electrical or pharmacological cardioversion is the most common approach in the Emergency Department (ED). However, considering the high percentage of spontaneous cardioversion of paroxysmal AF reported by many studies, this approach may not be the ideal choice for all patients. In this manuscript we performed a review of the most relevant studies found in literature with the aim of identifying the main determinants of spontaneous cardioversion, focusing on those easy to detect in the ED. We have found that the most relevant predictors of spontaneous cardioversion are the absence of Heart Failure (HF), a small atrial size, recent-onset AF, rapid Atrial Fibrillatory Rate and the relationship between a previous AF episode and Heart Rate/Blood Pressure. A number of those are utilized, along with other easily determined parameters, in the recently developed "ReSinus" score which predicts the likelihood of AF spontaneous cardioversion. Such identification may help the physician decide whether immediate cardioversion is necessary, or whether to adopt a "watch-and-wait" strategy in the presence of spontaneous cardioversion determinants.

Chest computed tomography score, cycle threshold values and secondary infection in predicting COVID-19 mortality.

This retrospective and observational cohort study investigated chest computed tomography (CT) findings, cycle threshold (Ct) values in RT-PCR of SARS-CoV-2 and secondary infection occurrence to predict prognosis in COVID-19 patients. At hospital admission, CT findings and Ct values were collected. Microbiology tests performed after 48 hours from hospitalization were reviewed. According to in-hospital mortality, patients were grouped into non-survivors and survivors. Among 283 patients evaluated, in-hospital mortality rate was 13.8% (39/283). Secondary infection occurrence was 15.2% (43/283). Cut-off values for CT score >13.5 (AUC=0.682 p=0.0009) and for Ct <23.4 (AUC=0.749, p<0.0001) were predictive of death. Super-additive and synergic effects between high CT score plus secondary infection occurrence as well as between high CT score plus low Ct values affecting patient's outcome were observed. Chest CT score and Ct values in RT-PCR of SARS-CoV-2 could have a combination role for severity stratification of COVID-19 patients.

Clinical impact of transient lymphopenia.

Transient or persistent immunosuppression is a known risk factor for morbidity and mortality in critically ill patients. Aim of the present study is to evaluate the lymphopenia in patients admitted to the Emergency Unit of AOU Policlinico Umberto I, to investigate its prevalence at admission and the persistence during hospitalization until discharge. Possible correlations were evaluated between lymphopenia, diagnosis of admission, comorbidities and chronic treatments. In this study, 240 patients (142 men; 98 female; mean age 75.1 ± 15.1) were enrolled. Patients were divided into two groups according to the lymphocytes count at hospital admission, namely "Group A" with lymphopenia and "Group B" with values in the normal range. Moreover, the patients in group A were distinguished in relation to the regression or persistence of the lymphopenia assessed at the time of hospital discharge (Group A1: persistence; Group A2: normalization). Prevalence of lymphopenia at admission was 57%; Group A showed higher mean age and percentage of patients over 65 years of age; and none differences were observed regarding gender. Prevalence of lymphopenia at admission was 57%; Group A showed higher mean age and percentage of patients over 65 years of age; no differences were observed regarding gender. All subsets of the lymphocytes (CD4+, CD8+, NK) were equally reduced. Persistent lymphopenia was found in 19% of patients. Lymphopenia should be valued at the time of hospital admission as a factor influencing the prognosis, the management and the treatment of these patients.

Neutrophil to lymphocyte ratio (NLR) and short-term mortality risk in elderly acute medical patients admitted to a University Hospital Emergency Department.

Early identification of patients with a poorer prognosis in the Emergency Department (ED) is crucial for prompt treatment and resource allocation. We investigated the relationship between the Neutrophil to Lymphocyte Ratio (NLR) and 30-day mortality in elderly acute medical patients. Prospective single-center cohort study including consecutive patients admitted to the ED. Inclusion criteria were age > 65 years and medical condition as the cause of ED access. Exclusion criteria were patients admitted for traumatic injuries or non-traumatic surgical diseases. ROC analysis was used to set the best cut-off of the NLR for mortality. 953 patients were included and 142 (14.9%) died during follow-up. ROC analysis showed a good predictive value of the NLR with an AUC 0.70, 95%CI 0.67-0.73 (p < 0.001) and identified a NLR > 8 as the best cut-off. Patients with NLR > 8 had a more serious triage code (72.6% had a triage code ≤ 2) and an increased heart rate and body temperature. They more often presented with dyspnea, abdominal pain, falls and vomiting. They also were characterized by an increase in urea, creatinine, white blood cells, neutrophils, fibrinogen, D-dimer, glycemia, CRP, LDH and transaminases and by a decrease in eGFR, of lymphocytes and monocytes. Multivariable logistic regression analysis demonstrated that the NLR remained associated with mortality after adjustment for confounders (Odds ratio 2.563, 95%CI 1.595-4.118, p < 0.001). Patients with NLR > 8 showed a higher mortality rate. NLR is an easy and inexpensive tool that may be used for risk stratification in the ED. The results of this study need to be validated in larger external cohorts.

Efficacy and Safety of Combination Therapy with Low-Dose Rivaroxaban in Patients with Cardiovascular Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Objectives: To review the evidence on the effectiveness and safety of low-dose-rivaroxaban 2.5 mg twice daily (LDR) in patients with coronary artery disease (CAD) and/or peripheral artery disease (PAD) taking antiplatelets. Methods: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs). Efficacy endpoints were cardiovascular events (CVEs), myocardial infarction, stroke, all-cause, and cardiovascular death. Any, major, fatal bleeding, and intracranial hemorrhage (ICH) were safety endpoints. Numbers needed to treat (NNT), and numbers needed to harm (NNH) were also calculated. Results: Seven RCTs were included with 45,836 patients: 34,276 with CAD and 11,560 with PAD. Overall, 4247 CVEs and 3082 bleedings were registered. LDR in association with either any antiplatelet drug or aspirin (ASA) alone reduced the risk of CVEs (hazard ratio [HR] 0.86, 95% confidence interval [95%CI] 0.78-0.94) and ischemic stroke (HR 0.68, 95%CI 0.55-0.84). LDR + ASA increased the risk of major bleeding (HR 1.71, 95%CI 1.38-2.11) but no excess of fatal bleeding or ICH was found. The NNT to prevent one CVE for LDR + ASA was 63 (43-103) and the NNH to cause major bleeding was 107 (77-193). Conclusions: The combination of LDR with either antiplatelet drugs or low-dose aspirin reduces CVEs and ischemic stroke in patients with CAD/PAD. There was an increased risk of major bleeding but no excess of fatal or ICH was found. LDR seems to have a favorable net clinical benefit compared to ASA treatment alone.

Blood Count and Renal Functionality Assessments in the Emergency Section Disclose Morbidity and Mortality in Omicron COVID-19 Patients: A Retrospective Study.

Background: SARS-CoV-2 is the coronavirus responsible for the COVID-19 pandemic. Even though we are no longer in a pandemic situation, people are still getting infected, some of them need hospitalization and a few of them die. Methods: We conducted a retrospective study including 445 patients who accessed the Emergency Section of Policlinico Umberto I, Rome, Italy, where they had routine blood exams. In this study, we focused on the complete blood count, serum creatinine and azotemia. The data were analyzed using ANOVA, Spearman correlation and ROC analyses. They were divided into four groups based on their clinical outcomes: (1) the emergency group (patients who had mild forms and were quickly discharged); (2) the hospital ward group (patients who were admitted to the emergency section and were then hospitalized in a COVID-19 ward); (3) the intensive care unit (ICU) group (patients who required intensive assistance after the admission in the emergency section); (4) the deceased group (patients who had a fatal outcome after admission to the emergency section). Results: We found significant changes for creatinine, azotemia, hematocrit, mean corpuscular hemoglobin concentration, basophils, monocytes, red blood cell distribution width, hemoglobin, hematocrit and red blood cell numbers using ANOVA according to their clinical outcomes, particularly for the deceased group. Also, we found linear correlations of clinical outcomes with eosinophils, hemoglobin, hematocrit, mean corpuscular hemoglobin concentration, lymphocyte, neutrophil, platelet and red blood cell number and red blood cell distribution width. Conclusions: This study discloses an early association between "classical" routine blood biomarkers and the severity of clinical outcomes in Omicron patients.

Association of proprotein convertase subtilisin/kexin type 9 (PCSK9) levels with abnormally high ankle-brachial index in atrial fibrillation.

BACKGROUND: High ankle-brachial index (ABI) has been associated with increased risk of worse outcomes in the general population. Few data on atrial fibrillation (AF) exist. Experimental data suggest that proprotein convertase subtilisin/kexin type 9 (PCSK9) contributes to vascular calcification but clinical data on this association are lacking. AIMS: We wanted to investigate the relationship between circulating PCSK9 levels and an abnormally high ABI in patients suffering from AF. METHODS: We analyzed data from 579 patients included in the prospective ATHERO-AF study. An ABI≥1.4 was considered high. PCSK9 levels were measured coincidentally with ABI measurement. We used optimized cut-offs of PCSK9 for both ABI and mortality obtained from Receiver Operator Characteristic (ROC) curve analysis. All-cause mortality according to the ABI value was also analyzed. RESULTS: One hundred and fifteen patients (19.9%) had an ABI ≥1.4. The mean (standard deviation [SD]) age was 72.1 (7.6) years, and 42.1% of patients were women. Patients with ABI ≥1.4 were older, more frequently male, and diabetic. Multivariable logistic regression analysis showed an association between ABI ≥1.4 and serum levels of PCSK9 > 1150 pg/ml (odds ratio [OR], 1.649; 95% confidence interval [CI], 1.047-2.598; P = 0.031). During a median follow-up of 41 months, 113 deaths occurred. In multivariable Cox regression analysis, an ABI ≥1.4 (hazard ratio [HR], 1.626; 95% CI, 1.024-2.582; P = 0.039), CHA2DS2-VASc score (HR, 1.249; 95% CI, 1.088-1.434; P = 0.002), antiplatelet drug use (HR, 1.775; 95% CI, 1.153-2.733; P = 0.009), and PCSK9 > 2060 pg/ml (HR, 2.200; 95% CI, 1.437-3.369; P < 0.001) were associated with all-cause death. CONCLUSIONS: In AF patients, PCSK9 levels relate to an abnormally high ABI ≥1.4. Our data suggest PCSK9 role in contributing to vascular calcification in AF patients.

Interleukin 18 and IL-18 BP response to Sars-CoV-2 virus infection.

The immune response to the SARS-CoV-2 infection is crucial to the patient outcome. IL-18 is involved in the lymphocyte response to the disease and it is well established its important role in the complex developing of the host response to viral infection. This study aims at the analysis of the concentrations of IL-18, IL-18BP, INF-γ at the onset of the SARS-CoV-2 infection. The serum levels of measured interleukins were obtained through enzyme-linked immunosorbent assay. Furthermore, the free fraction of IL-18 was numerically evaluated. The enrolled patients were divided in two severity groups according to a threshold value of 300 for the ratio of arterial partial pressure of oxygen and fraction of inspired oxygen fraction and according to the parenchymal involvement as evaluated by computerized tomography at the admittance. In the group of patients with a more severe disease, a significant increase of the IL-18, INF-γ and IL-18BP levels have been observed, whereas the free IL-18 component values were almost constant. The results confirm that, at the onset of the disease, the host response keep the inflammatory cytokines in an equilibrium and support the hypothesis to adopt the IL-18BP modulation as a possible and effective therapeutic approach.

Direct or early Discharge of Acute Bacterial Skin and Skin Structure Infection patients from the Emergency Department/Unit: place in therapy of dalbavancin.

INTRODUCTION: Acute Bacterial Skin and Skin Structure Infections (ABSSSIs) are a common reason of Emergency Department (ED) access and account for a considerable number of hospital admissions and a high economic burden for the healthcare system. The long-acting lipoglycopeptides (LALs) allow for an outpatient management of subjects with ABSSSIs, still requiring parenteral therapy, but who do not need hospitalization. AREAS COVERED: The following topics were addressed: i) microbiological activity, efficacy, and safety of dalbavancin, ii) critical steps for the management of ABSSSIs in the ED (decision to hospitalize, risk of bacteremia and infection recurrence), iii) feasibility of direct/early discharge from the ED and potential advantage of dalbavancin. EXPERT OPINION: Authors' expert opinion was focused on drawing the profiles of patients who could benefit most from an antimicrobial therapy with dalbavancin in the ED and positioning this drug as a direct or early discharge strategy from the ED in order to avoid hospitalization and its complications. We have provided a therapeutic and diagnostic algorithm based on evidence from the literature and authors' expert opinion and suggest the use of dalbavancin in patients with ABSSSIs who are not eligible for oral therapies or Outpatient Parenteral Antibiotic Therapy (OPAT) programs and who would have otherwise been hospitalized only for antibiotic therapy.

Pulmonary embolism post-Covid-19 infection: physiopathological mechanisms and vascular damage biomarkers.

Covid-19 infection is characterized by several acute complications, as well long-term sequelae, mostly sustained by endothelial dysfunction; several studies show that complications as pulmonary embolism (PE) are described both in the acute phase and after negativization. Aim of research was to evaluate anthropometric, bio-humoral, instrumental parameters in a group of patients affected by PE after recent Covid-19 infection compared to PE patients without previous Covid-19 infection. We enrolled 72 consecutive patients (35M, 37F) with acute PE, distinguished in relation to previous acute Covid-19 infection: 54 pts without previous acute Covid-19 infection and 18 pts with previous Covid-19 infection within negativity at least 2 months before PE diagnosis; 44 healthy subjects (21M, 23F) were recruited as control group. Patients who had previously developed Covid-19 needed hospitalization in high percentage (84%); this group showed significantly higher prevalence of diabetes mellitus than Covid-19-free PE patients, reduced serum levels of C-reactive protein, sST2 and PESI score. In post-Covid-19 PE group, we observed higher mean IMPROVE risk score, whereas in Covid-19-free group lower P/F ratio, higher radiological severity, and worse PESI score and severity index. Covid-19 infection affects not just the lung parenchyma but also other organs; endothelial damage plays pivotal role in long-term alterations; in high thrombotic risk group (recent hospitalization due to acute Covid-19 infection), we have described thrombotic complications characterized by persistent prothrombotic state after recovery, highlighted by well-known markers as PCR and D-Dimer as well as novel vascular marker (sST2).

Blood Biomarkers from the Emergency Department Disclose Severe Omicron COVID-19-Associated Outcomes.

BACKGROUND: Since its outbreak, Coronavirus disease 2019 (COVID-19), a life-threatening respiratory illness, has rapidly become a public health emergency with a devastating social impact. Lately, the Omicron strain is considered the main variant of concern. Routine blood biomarkers are, indeed, essential for stratifying patients at risk of severe outcomes, and a huge amount of data is available in the literature, mainly for the previous variants. However, only a few studies are available on early routine biochemical blood biomarkers for Omicron-afflicted patients. Thus, the aim and novelty of this study were to identify routine blood biomarkers detected at the emergency room for the early prediction of severe morbidity and/or mortality. METHODS: 449 COVID-19 patients from Sapienza University Hospital of Rome were divided into four groups: (1) the emergency group (patients with mild forms who were quickly discharged); (2) the hospital ward group (patients that after the admission in the emergency department were hospitalized in a COVID-19 ward); (3) the intensive care unit (ICU) group (patients that after the admission in the emergency department required intensive assistance); (4) the deceased group (patients that after the admission in the emergency department had a fatal outcome). RESULTS: ANOVA and ROC data showed that high-sensitivity troponin-T (TnT), fibrinogen, glycemia, C-reactive protein, lactate dehydrogenase, albumin, D-dimer myoglobin, and ferritin for both men and women may predict lethal outcomes already at the level of the emergency department. CONCLUSIONS: Compared to previous Delta COVID-19 parallel emergency patterns of prediction, Omicron-induced changes in TnT may be considered other early predictors of severe outcomes.

Reduced Reliability of Procalcitonin (PCT) as a Biomarker of Bacterial Superinfection: Concerns about PCT-Driven Antibiotic Stewardship in Critically Ill COVID-19 Patients-Results from a Retrospective Observational Study in Intensive Care Units.

BACKGROUND: The aim of this study was to assess whether procalcitonin levels is a diagnostic tool capable of accurately identifying sepsis and ventilator-associated pneumonia (VAP) even in critically ill COVID-19 patients. METHODS: In this retrospective, observational study, all critically ill COVID-19 patients who survived for ≥2 days in a single university hospital and had at least one serum procalcitonin (PCT) value and associated blood culture and/or culture from a lower respiratory tract specimen available were eligible for the study. RESULTS: Over the research period, 184 patients were recruited; 67 VAP/BSI occurred, with an incidence rate of 21.82 episodes of VAP/BSI (95% CI: 17.18-27.73) per 1000 patient-days among patients who were included. At the time of a positive microbiological culture, an average PCT level of 1.25-3.2 ng/mL was found. Moreover, also in subjects without positive cultures, PCT was altered in 21.7% of determinations, with an average value of 1.04-5.5 ng/mL. Both PCT and PCT-72 h were not linked to a diagnosis of VAP/BSI in COVID-19 patients, according to the multivariable GEE models (aOR 1.13, 95% CI 0.51-2.52 for PCT; aOR 1.32, 95% CI 0.66-2.64 for PCT-72 h). CONCLUSION: Elevated PCT levels might not always indicate bacterial superinfections or coinfections in a severe COVID-19 setting.

Tissue Inhibitor of Matrix Metalloproteinases-1 (TIMP-1) and Pulmonary Involvement in COVID-19 Pneumonia.

Background: The aim of the study was to longitudinally evaluate the association between MMP-2, MMP-9, TIMP-1 and chest radiological findings in COVID-19 patients. Methods: COVID-19 patients were evaluated based on their hospital admission (baseline) and three months after hospital discharge (T post) and were stratified into ARDS and non-ARDS groups. As a control group, healthy donors (HD) were enrolled. Results: At the baseline, compared to HD (n = 53), COVID-19 patients (n = 129) showed higher plasma levels of MMP-9 (p < 0.0001) and TIMP-1 (p < 0.0001) and the higher plasma activity of MMP-2 (p < 0.0001) and MMP-9 (p < 0.0001). In the ARDS group, higher plasma levels of MMP-9 (p = 0.0339) and TIMP-1 (p = 0.0044) and the plasma activity of MMP-2 (p = 0.0258) and MMP-9 (p = 0.0021) compared to non-ARDS was observed. A positive correlation between the plasma levels of TIMP-1 and chest computed tomography (CT) score (ρ = 0.2302, p = 0.0160) was observed. At the T post, a reduction in plasma levels of TIMP-1 (p < 0.0001), whereas an increase in the plasma levels of MMP-9 was observed (p = 0.0088). Conclusions: The positive correlation between TIMP-1 with chest CT scores highlights its potential use as a marker of fibrotic burden. At T post, the increase in plasma levels of MMP-9 and the reduction in plasma levels of TIMP-1 suggested that inflammation and fibrosis resolution were still ongoing.

Biomarkers of Neurological Damage: From Acute Stage to Post-Acute Sequelae of COVID-19.

Background: Neurological symptoms (NS) in COVID-19 are related to both acute stage and long-COVID. We explored levels of brain injury biomarkers (NfL and GFAP) and myeloid activation marker (sCD163) and their implications on the CNS. Materials and Methods: In hospitalized COVID-19 patients plasma samples were collected at two time points: on hospital admission (baseline) and three months after hospital discharge (Tpost). Patients were stratified according to COVID-19 severity based on acute respiratory distress syndrome (ARDS) onset (severe and non-severe groups). A further stratification according to the presence of NS (with and without groups) at baseline (requiring a puncture lumbar for diagnostic purposes) and according to NS self-referred at Tpost was performed. Finally, cerebrospinal fluid (CSF) samples were collected from patients with NS present at baseline. Results: We enrolled 144 COVID-19 patients (62 female/82 male; median age [interquartile range, IQR]): 64 [55-77]) and 53 heathy donors (HD, 30 female/23 male; median age [IQR]: 64 [59-69]). At baseline, higher plasma levels of NfL, GFAP and sCD163 in COVID-19 patients compared to HD were observed (p < 0.0001, p < 0.0001 and p < 0.0001, respectively), especially in those with severe COVID-19 (p < 0.0001, p < 0.0001 and p < 0.0001, respectively). Patients with NS showed higher plasma levels of NfL, GFAP and sCD163 compared to those without (p = 0.0023, p < 0.0001 and 0.0370, respectively). At baseline, in COVID-19 patients with NS, positive correlations between CSF levels of sCD163 and CSF levels of NfL (ρ = 0.7536, p = 0.0017) and GFAP were observed (ρ = 0.7036, p = 0.0045). At Tpost, the longitudinal evaluation performed on 77 COVID-19 patients showed a significant reduction in plasma levels of NfL, GFAP and sCD163 compared to baseline (p < 0.0001, p < 0.0001 and p = 0.0413, respectively). Finally, at Tpost, in the severe group, higher plasma levels of sCD163 in patients with NS compared to those without were reported (p < 0.0001). Conclusions: High plasma levels of NfL, GFAP and sCD163 could be due to a proinflammatory systemic and brain response involving microglial activation and subsequent CNS damage. Our data highlight the association between myeloid activation and CNS perturbations.

Fibrosis-4 (FIB-4) Index and mortality in COVID-19 patients admitted to the emergency department.

Liver damage worsens the prognosis of coronavirus 19 disease (COVID-19). However, the best strategy to stratify mortality risk according to liver damage has not been established. The aim of this study is to test the predictive value of the validated Fibrosis-4 (FIB-4) Index and compared it to liver transaminases and to the AST-to-Platelet ratio index (APRI). Multicenter cohort study including 992 consecutive COVID-19 patients admitted to the Emergency Department. FIB-4 > 3.25 and APRI > 0.7 were used to define liver damage. Multivariable Cox regression and ROC curve analysis for mortality were performed. Secondary endpoints were (1) need for high-flow oxygen and (2) mechanical ventilation. 240 (24.2%) patients had a FIB-4 > 3.25. FIB-4 > 3.25 associated with an increased mortality (n = 119, log-rank test p < 0.001 and adjusted hazard ratio (HR) 1.72 (95% confidence interval [95%CI] 1.14-2.59, p = 0.010). ROC analysis for mortality showed that FIB-4 (AUC 0.734, 95% CI 0.705-0.761) had a higher predictive value than AST (p = 0.0018) and ALT (p < 0.0001). FIB-4 > 3.25 was also superior to APRI > 0.7 (AUC 0.58, 95% CI 0.553-0.615, p = 0.0008). Using an optimized cut-off > 2.76 (AUC 0.689, 95% CI 0.659-0.718, p < 0.0001), FIB-4 was superior to FIB-4 > 3.25 (p = 0.0302), APRI > 0.7 (p < 0.0001), AST > 51 (p = 0.0119) and ALT > 42 (p < 0.0001). FIB-4 was also associated with high-flow oxygen use (n = 255, HR 1.69, 95% CI 1.25-2.28, p = 0.001) and mechanical ventilation (n = 39, HR 2.07, 95% CI 1.03-4.19, p = 0.043). FIB-4 score predicts mortality better than liver transaminases and APRI score. FIB-4 score may be an easy tool to identify COVID-19 patients at worse prognosis in the emergency department.

Risk of Seven-Day Worsening and Death: A New Clinically Derived COVID-19 Score.

This monocentric, retrospective, two-stage observational study aimed to recognize the risk factors for a poor outcome in patients hospitalized with SARS-CoV-2 infection, and to develop and validate a risk score that identifies subjects at risk of worsening, death, or both. The data of patients with SARS-CoV-2 infection during the first wave of the pandemic were collected and analyzed as a derivation cohort. Variables with predictive properties were used to construct a prognostic score, which was tried out on a validation cohort enrolled during the second wave. The derivation cohort included 494 patients; the median age was 62 and the overall fatality rate was 22.3%. In a multivariable analysis, age, oxygen saturation, neutrophil-to-lymphocyte ratio, C-reactive protein and lactate dehydrogenase were independent predictors of death and composed the score. A cutoff value of 3 demonstrated a sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) of 93.5%, 68.5%, 47.4% and 97.2% for death, and 84.9%, 84.5%, 79.6% and 87.9% for worsening, respectively. The validation cohort included 415 subjects. The score application showed a Se, Sp, PPV and NPV of 93.4%, 61.6%, 29.5% and 98.1% for death, and 81%, 76.3%, 72.1% and 84.1% for worsening, respectively. We propose a new clinical, easy and reliable score to predict the outcome in hospitalized SARS-CoV-2 patients.