Lung involvement in macrophage activation syndrome and severe COVID-19: results from a cross-sectional study to assess clinical, laboratory and artificial intelligence-radiological differences.

OBJECTIVES: To evaluate the clinical pictures, laboratory tests and imaging of patients with lung involvement, either from severe COVID-19 or macrophage activation syndrome (MAS), in order to assess how similar these two diseases are. METHODS: The present work has been designed as a cross-sectional single-centre study to compare characteristics of patients with lung involvement either from MAS or severe COVID-19. Chest CT scans were assessed by using an artificial intelligence (AI)-based software. RESULTS: Ten patients with MAS and 47 patients with severe COVID-19 with lung involvement were assessed. Although all patients showed fever and dyspnoea, patients with MAS were characterised by thrombocytopaenia, whereas patients with severe COVID-19 were characterised by lymphopaenia and neutrophilia. Higher values of H-score characterised patients with MAS when compared with severe COVID-19. AI-reconstructed images of chest CT scan showed that apical, basal, peripheral and bilateral distributions of ground-glass opacities (GGOs), as well as apical consolidations, were more represented in severe COVID-19 than in MAS. C reactive protein directly correlated with GGOs extension in both diseases. Furthermore, lymphopaenia inversely correlated with GGOs extension in severe COVID-19. CONCLUSIONS: Our data could suggest laboratory and radiological differences between MAS and severe COVID-19, paving the way for further hypotheses to be investigated in future confirmatory studies.

Relative lymphocyte count as an indicator of 3-year mortality in elderly people with severe COPD.

BACKGROUND: Prognostic stratification of elderly patients with chronic obstructive pulmonary disease (COPD) is difficult due to the wide inter-individual variability in the course of the disease. No marker can exactly stratify the evolution and natural history of COPD patients. Studies have shown that leukocyte count is associated with increased risk of mortality in COPD patients. The aim of this study was to evaluate the possible role of relative lymphocyte count as a risk marker for mortality in elderly patients with COPD. METHODS AND RESULTS: This is a3-year prospective study. A total of 218patients, mean age 75.2±7 years, with moderate to severe COPD and free from conditions affecting lymphocyte count were enrolled. The population was divided into two groups according to the relative lymphocyte count, with a cut-off of 20%. Eighty-five patients (39%) had a relative lymphocyte count ≤20%. Three-year mortality rates from any cause in patients with relative lymphocyte count ≤ or > 20% were 68 and 51%, respectively (p = 0.0012). Survival curve analysis showed higher mortality in patients with relative lymphocyte count ≤20% (p = 0.0005). After adjustment for age and sex, the hazard ratio for mortality risk according to lymphocyte count was 1.79 (95% confidence interval [CI]: 1.26-2.57, p = 0.0013), even in the analysis limited to the 171 patients without congestive heart failure (1.63; 95% CI: 1.03-2.58, p = 0.038). CONCLUSIONS: Low relative lymphocyte count was associated with higher mortality in elderly patients with severe COPD.

Post-Procedural Follow-Up of the Interventional Radiology's Management of Osteoid Osteomas and Osteoblastomas.

The family of painful osteocytic tumors includes osteoblastomas and osteoid osteomas-these lesions are considered benign, but they could produce a significant painful symptomatology. Usually, people affected are between 20 s and 30 s. When symptomatic, an effective treatment is mandatory for the management of these lesions to allow for a ful quality of life. The possibilities of treatment range from chirurgical en-block resection (procedure of surgical oncology aiming to remove a tumoral mass in its entirety, completely surrounded by a continuous layer of healthy tissue) to interventional approaches that, nowadays, are considered the most affordable and sustainable in terms of effectiveness, recovery after procedure, and for bone structure sparing. The main techniques used for osteoid osteomas and osteoblastomas are radio frequency ablation (RFA) and magnetic resonance-guided focused ultrasound (MRgFUS): the most important difference between these approaches is the needleless approach of MRgFUS, which further reduces the minimal invasiveness of RFA (and the related consequences) and the absence of exposure to ionizing radiation. Despite their high efficacy, a recurrence of pathology may occur due to a failure in therapy. In light of this, describing the various possibilities of follow up protocols and the imaging aspects of recurrence or incomplete treatment is mandatory. In the scenario given in the literature, many authors have tried to asses an organized follow up protocol of these patients, but many of them did not undergo periodical magnetic resonance (MR) or computerized tomography (CT) because of the lack of symptomatology. However, even if it seems that clinical evolution is central, different papers describe the protocol useful to detect eventual relapse. The aim of our manuscript is to review the various possibilities of follow-up of these patients and to bring together the most salient aspects found during the management of these osteocytic bone lesions.

Impaired Vagal Activity in Long-COVID-19 Patients.

Long-COVID-19 refers to the signs and symptoms that continue or develop after the "acute COVID-19" phase. These patients have an increased risk of multiorgan dysfunction, readmission, and mortality. In Long-COVID-19 patients, it is possible to detect a persistent increase in D-Dimer, NT-ProBNP, and autonomic nervous system dysfunction. To verify the dysautonomia hypothesis in Long-COVID-19 patients, we studied heart rate variability using 12-lead 24-h ECG monitoring in 30 Long-COVID-19 patients and 20 No-COVID patients. Power spectral analysis of heart rate variability was lower in Long-COVID-19 patients both for total power (7.46 ± 0.5 vs. 8.08 ± 0.6; p < 0.0001; Cohens-d = 1.12) and for the VLF (6.84 ± 0.8 vs. 7.66 ± 0.6; p < 0.0001; Cohens-d = 1.16) and HF (4.65 ± 0.9 vs. 5.33 ± 0.9; p = 0.015; Cohens-d = 0.76) components. The LF/HF ratio was significantly higher in Long-COVID-19 patients (1.46 ± 0.27 vs. 1.23 ± 0.13; p = 0.001; Cohens-d = 1.09). On multivariable analysis, Long-COVID-19 is significantly correlated with D-dimer (standardized ß-coefficient = 0.259), NT-ProBNP (standardized ß-coefficient = 0.281), HF component of spectral analysis (standardized ß-coefficient = 0.696), and LF/HF ratio (standardized ß-coefficient = 0.820). Dysautonomia may explain the persistent symptoms in Long COVID-19 patients. The persistence of a procoagulative state and an elevated myocardial strain could explain vagal impairment in these patients. In Long-COVID-19 patients, impaired vagal activity, persistent increases of NT-ProBNP, and a prothrombotic state require careful monitoring and appropriate intervention.

Heart Failure and Cardiomyopathies: CT and MR from Basics to Advanced Imaging.

Since 1997, heart failure (HF) has been designated as a new epidemic. However, it is not easy to find a proper definition since different descriptors are used in clinical practice. Moreover, HF is not a single clinical entity, and there is a close relationship between HF and all cardiomyopathies (CMs). This leads us to also consider accuracy in the characterization of CMs, which is essential to define the therapeutic process of HF patients. This narrative review aims to describe the main mechanisms leading to HF in different CMs, as well as the current diagnostic and prognostic advantages deriving from advanced imaging in the cardiac field.

The Cross-Talk between Thrombosis and Inflammatory Storm in Acute and Long-COVID-19: Therapeutic Targets and Clinical Cases.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) commonly complicates with coagulopathy. A syndrome called Long-COVID-19 is emerging recently in COVID-19 survivors, characterized, in addition to the persistence of symptoms typical of the acute phase, by alterations in inflammatory and coagulation parameters due to endothelial damage. The related disseminated intravascular coagulation (DIC) can be associated with high death rates in COVID-19 patients. It is possible to find a prothrombotic state also in Long-COVID-19. Early administration of anticoagulants in COVID-19 was suggested in order to improve patient outcomes, although exact criteria for their application were not well-established. Low-molecular-weight heparin (LMWH) was commonly adopted for counteracting DIC and venous thromboembolism (VTE), due to its pharmacodynamics and anti-inflammatory properties. However, the efficacy of anticoagulant therapy for COVID-19-associated DIC is still a matter of debate. Thrombin and Factor Xa (FXa) are well-known components of the coagulation cascade. The FXa is known to strongly promote inflammation as the consequence of increased cytokine expression. Endothelial cells and mononuclear leucocytes release cytokines, growth factors, and adhesion molecules due to thrombin activation. On the other hand, cytokines can activate coagulation. The cross-talk between coagulation and inflammation is mediated via protease-activated receptors (PARs). These receptors might become potential targets to be considered for counteracting the clinical expressions of COVID-19. SARS-CoV-2 is effectively able to activate local and circulating coagulation factors, thus inducing the generation of disseminated coagula. LMWH may be considered as the new frontier in the treatment of COVID-19 and Long-COVID-19. Indeed, direct oral anticoagulants (DOACs) may be an alternative option for both early and later treatment of COVID-19 patients due to their ability to inhibit PARs. The aim of this report was to evaluate the role of anticoagulants-and DOACs in particular in COVID-19 and Long-COVID-19 patients. We report the case of a COVID-19 patient who, after administration of enoxaparin developed DIC secondary to virosis and positivity for platelet factor 4 (PF4) and a case of Long-COVID with high residual cardiovascular risk and persistence of blood chemistry of inflammation and procoagulative state.

A Systematic Review of the Efficacy and Safety of Direct Oral Anticoagulants in Atrial Fibrillation Patients with Diabetes Using a Risk Index.

Diabetes mellitus (DM) represents an independent risk factor for chronic AF and is associated with unfavorable outcomes. We aimed to evaluate the efficacy and safety of direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF), with and without diabetes mellitus (DM), using a new risk index (RI) defined as: RI =Rate of EventsRate of Patients at Risk. In particular, an RI lower than 1 suggests a favorable treatment effect. We searched MEDLINE, MEDLINE In-Process, EMBASE, PubMed, and the Cochrane Central Register of Controlled Trials. The risk index (RI) was calculated in terms of efficacy (rate of stroke/systemic embolism (stroke SEE)/rate of patients with and without DM; rate of cardiovascular death/rate of patients with and without DM) and safety (rate of major bleeding/rate of patients with and without DM) outcomes. AF patients with DM (n = 22,057) and 49,596 without DM were considered from pivotal trials. DM doubles the risk index for stroke/SEE, major bleeding (MB), and cardiovascular (CV) death. The RI for stroke/SEE, MB, and CV death was comparable in patients treated with warfarin or DOACs. The lowest RI was in DM patients treated with Rivaroxaban (stroke/SEE, RI = 0.08; CV death, RI = 0.13). The RIs for bleeding were higher in DM patients treated with Dabigatran (RI110 = 0.32; RI150 = 0.40). Our study is the first to use RI to homogenize the efficacy and safety data reported in the DOACs pivotal studies against warfarin in patients with and without DM. Anticoagulation therapy is effective and safe in DM patients. DOACs appear to have a better efficacy and safety profile than warfarin. The use of DOACs is a reasonable alternative to vitamin-K antagonists in AF patients with DM. The RI can be a reasonable tool to help clinicians choose between DOACs or warfarin in the peculiar set of AF patients with DM.

Automated Quantitative Lung CT Improves Prognostication in Non-ICU COVID-19 Patients beyond Conventional Biomarkers of Disease.

(1) Background: COVID-19 continues to represent a worrying pandemic. Despite the high percentage of non-severe illness, a wide clinical variability is often reported in real-world practice. Accurate predictors of disease aggressiveness, however, are still lacking. The purpose of our study was to evaluate the impact of quantitative analysis of lung computed tomography (CT) on non-intensive care unit (ICU) COVID-19 patients' prognostication; (2) Methods: Our historical prospective study included fifty-five COVID-19 patients consecutively submitted to unenhanced lung CT. Primary outcomes were recorded during hospitalization, including composite ICU admission for the need of mechanical ventilation and/or death occurrence. CT examinations were retrospectively evaluated to automatically calculate differently aerated lung tissues (i.e., overinflated, well-aerated, poorly aerated, and non-aerated tissue). Scores based on the percentage of lung weight and volume were also calculated; (3) Results: Patients who reported disease progression showed lower total lung volume. Inflammatory indices correlated with indices of respiratory failure and high-density areas. Moreover, non-aerated and poorly aerated lung tissue resulted significantly higher in patients with disease progression. Notably, non-aerated lung tissue was independently associated with disease progression (HR: 1.02; p-value: 0.046). When different predictive models including clinical, laboratoristic, and CT findings were analyzed, the best predictive validity was reached by the model that included non-aerated tissue (C-index: 0.97; p-value: 0.0001); (4) Conclusions: Quantitative lung CT offers wide advantages in COVID-19 disease stratification. Non-aerated lung tissue is more likely to occur with severe inflammation status, turning out to be a strong predictor for disease aggressiveness; therefore, it should be included in the predictive model of COVID-19 patients.

Diagnostic and interventional radiology fundamentals of synovial pathology.

The synovial membrane is a specialized mesenchymal tissue that lines the diarthrodial joints surfaces, bursae, and tendon sheaths of the body. This article aims to provide an overview of the fundamentals of synovial tissue, with particular regard to the imaging findings of the main pathologic processes that can affect the synovia and the role of image-guided interventions.

Early Initiation of Sacubitril/Valsartan in Patients with Chronic Heart Failure After Acute Decompensation: A Case Series Analysis.

BACKGROUND AND OBJECTIVE: Sacubitril/valsartan improved the prognosis of patients with heart failure with reduced ejection fraction in the PARADIGM-HF study. Recently, the TRANSITION and PIONEER-HF studies demonstrated the safety and efficacy of sacubitril/valsartan in patients hospitalized for acute decompensated heart failure, with treatment initiated after hemodynamic and clinical stabilization. In this case series study, we assessed the short-term effects of sacubitril/valsartan on exercise capacity, inflammation, and biomarkers in patients with acute decompensated heart failure. METHODS: Patients admitted for acute decompensated heart failure to the Department of Internal Medicine of Telese Terme Hospital and Cardiovascular Department, University of Bari, from 9 March, 2017 to 9 June, 2018 were enrolled. Following hemodynamic stabilization, patients initiated sacubitril/valsartan 24/26 mg twice a day for 4 weeks, with up-titration to 49/51 mg twice a day based on tolerability after 1 week. Efficacy outcomes included the 6-min walking test, N-terminal pro-B-type natriuretic peptide, high-sensitivity C-reactive protein, and lymphocyte count. Safety outcomes included renal function, hyperkalemia, and symptomatic hypotension. RESULTS: In total, 40 patients completed the study and 27 (67.5%) patients were up-titrated. Compared with baseline, exercise capacity and relative lymphocyte count increased significantly after 4 weeks of treatment, while N-terminal pro-B-type natriuretic peptide and high-sensitivity C-reactive protein decreased significantly. N-terminal pro-B-type natriuretic peptide and relative lymphocyte count independently predicted the 6-min walking test distance (p = 0.021). No patients experienced any relevant side effects. CONCLUSIONS: Early initiation of sacubitril/valsartan in patients with heart failure with reduced ejection fraction after acute decompensated heart failure may be safe and effective in terms of functional capacity and biomarkers.

Efficacy and Safety of Direct Oral Anticoagulants in Patients With Atrial Fibrillation and High Thromboembolic Risk. A Systematic Review.

Background: The aim of the study was to evaluate the efficacy and safety of direct oral anticoagulants (DOACs) in a subgroup of patients with atrial fibrillation (AF), CHADS2 score ≥3, advanced age, and heart failure (HF) coming from the main DOACs randomized clinical trials. Methods: We searched MEDLINE, MEDLINE In-Process, and Other Non-Indexed Citations, EMBASE, PubMed, and the Cochrane Central Register of Controlled Trials. English-language articles published from 2002 to March 2019 dealing with DOACs for preventing thrombotic events in AF were considered. We did not conduct any statistical analyses, as indirect comparison between DOACs represents hypothesis generators. Results: This systematic review was restricted to the subgroup of patients with CHADS2 score ≥3 (n = 31,203), elderly (n = 24,788), and with HF (n = 29,297) derived from the pivotal trials. Risk index (RI) was calculated. The RI for stroke/systemic embolism was similar in all of the patients treated with DOACs or warfarin. The lowest RI was in rivaroxaban patients (CHADS2 score ≥3: RI = 0.04; elderly: RI = 0.09; HF: RI = 0.05). The RIs for bleeding were higher in patients treated with dabigatran (CHADS2 score ≥3: RI110 = 0.23; elderly: RI110 = 0.22; HF: RI110 = 0.16; CHADS2score ≥3: RI150 = 0.30; elderly: RI150 = 0.24; HF: RI150 = 0.16). The bleeding RIs were higher with apixaban (CHADS2 score ≥3: RI = 0.23; elderly: RI = 0.25; HF: RI = 0.14) and dabigatran (CHADS2 score ≥3: RI = 0.28; elderly: RI = 0.21; HF: RI = 0.19). Conclusions: The use of DOACs is a reasonable alternative to vitamin K antagonists in AF patients with CHADS2 score ≥3, advanced age, and HF. The RI constitutes a useful, additional tool to facilitate clinicians in choosing DOACs or warfarin in particular category of AF patients.

Safety and Feasibility of Treatment with Rivaroxaban for Non-Canonical Indications: A Case Series Analysis.

BACKGROUND AND OBJECTIVES: The new oral anticoagulants (NOACs) are used for the prevention of thromboembolic complications in patients with non-valvular atrial fibrillation (AF) and those at risk of deep venous thrombosis. Their rapid onset of action and predictable pharmacokinetic and pharmacodynamic profiles make them the optimal alternative to warfarin in the treatment of these two categories of patients. Unfortunately, however, NOACs cannot be used in patients with valvular AF or valvular cardiac prostheses. Although mechanical valves are effectively a contraindication to NOAC use due to several pathophysiological mechanisms that promote the use of warfarin rather than NOACs, few data exist regarding the use of such new pharmacological compounds on patients with cardiac biological valves or those who have undergone mitral repair or tubular aortic graft implantation. METHODS: Our case series involved 27 patients [mean age 70 ± 10 years; mean CHA2DS2-VASc (Congestive heart failure, Hypertension, Age ≥75 years (doubled), Diabetes mellitus, Stroke/transient ischemic attack (doubled), Vascular disease, Age 65-74 years, Sex category): 6 ± 1.4; and mean HAS-BLED (Hypertension, Abnormal renal and liver function, Stroke, Bleeding, Labile international normalized ratios, Elderly, Drugs or alcohol): 4 ± 1] with AF and biological prostheses, repaired mitral valves, or tubular aortic graft who were treated with the factor Xa inhibitor rivaroxaban due to inefficacy or adverse effects of warfarin. RESULTS: The mean left ventricular ejection fraction was 48 ± 9 %, the left atrial diameter was 46.5 ± 7 mm, and the estimated glomerular filtration rate was 45 ± 21 mL/min/1.73 m(2). The mean duration of treatment was 15 ± 2 months. No relevant complications or recurrent thromboembolic events occurred. Three patients had recurrent nose bleeding and two had hematuria that led to reduction of the rivaroxaban dose by the treating physician to 15 mg once a day after 4 months of therapy. No further bleeding episode was recorded after escalating the dose. CONCLUSIONS: Rivaroxaban is a valuable treatment option for patients with biological prostheses, repaired mitral valves, or a tubular aortic graft in order to prevent thromboembolic complications.

Exercise training effects on elderly and middle-age patients with chronic heart failure after acute decompensation: A randomized, controlled trial.

BACKGROUND: The aim of this study was to evaluate the effect of exercise training on cardiac function in heart failure (HF) patients recently suffering from acute decompensation. Radionuclide ambulatory ventricular function monitoring (VEST) was used to detect variations in cardiac hemodynamics during training period. METHODS: This was a monocentric, randomized, controlled trial. We enrolled 72 HF patients [left ventricle ejection fraction (LVEF) <40%] within two weeks after acute cardiogenic pulmonary edema: 40 in the elderly group, 32 in the middle-aged group. Trained patients underwent a specific four-weeks exercise program (closed-chain resistive activities and abdominal exercises) which was supervised by a therapist in agreement with patients' characteristics. Catecholamines at rest, echocardiography, right-heart catheterization, and bicycle ergometer were performed. VEST was performed at the end of the 4weeks-training in all patients in order to assess patients' cardiac hemodynamics [LVEF, cardiac output (CO), stroke volume]. RESULTS: Exercise training significantly improved exercise duration, peak oxygen consumption, and ventilatory threshold both in elderly and middle-aged patients (p<0.0001) after the 4-week controlled training. Despite age (F=35.086, p<0.0001; F=16.967, p<0.0001; F=42.574, p=0.03, respectively), training reliably influence previous cardiopulmonary parameters (F=29.402, F=16.421, F=26.80, p<0.0001, respectively). Norepinephrine and epinephrine were significantly reduced in both trained groups. Peak LVEF (37.3±4.7% vs 34±6.2%, p=0.002), peak stroke volume (43.3±3.9% vs 37.5±4.3%, p=0.001), and peak CO (63.4±6.1% vs 48.2±4.7%, p<0.0001) increased in middle-aged patients after 4-week training. CONCLUSIONS: Exercise training improves cardiac performance indexes and pulmonary function in both middle-aged and elderly HF patients early after an acute episode of cardiac decompensation.