Extracellular volume quantification in Cardiac CT: a new marker of cardiovascular risk in HIV positive individuals?

Inflammation in response to infection and injury is a critical survival mechanism used by all higher vertebrates. Chronic inflammatory conditions are associated with the prolongerelease of inflammatory mediators and the activation of harmful signal transduction pathways, all of which contribute disease development and phenotypes. Extracellular Volume Fraction (ECV) may be able to detect subtle abnormalities such as diffuse inflammation acute or chronic due to infection and/or fibrosis. The validity of this technique was preliminarily evaluated in a study with 20 patients suspected to have diffuse inflammation in the myocardial tissue. Using HU (Hounsfield Unit) values before and after administration of an Extracellular Contrast Agent (ECA) allows the additional calculation of the ECV, well established in CT. In fact, the ratio of the change in blood and tissue attenuation (HU) represents the contrast agent partition coefficient. People living with HIV (PLWH) have an increase vulnerability to sub-clinical and clinical cardiovascular (CV) diseases. Purpose: PLWH are prone to develop sub-clinical Cardiovascular (sCV) disease, despite the effectiveness of combined AntiRetroviral Therapy (cART). Algorithms developed to predict CV risk in the general population could be inaccurate when applied to PLWH. Myocardial Extra-Cellular Matrix (ECM) expansion, measured by computed tomography, has been associated with an increased CV vulnerability in HIV-negative population. Measurement of Myocardial ECV by computed tomography or magnetic resonance, is considered a useful surrogate for clinical evaluation of ECM expansion. In the present study, we aimed to determine the extent of cardiovascular involvement in asymptomatic HIV-infected patients with the use of a comprehensive cardiac computed tomography (CCT) approach. In this study, ECV in low atherosclerotic CV risk PLWH was compared with ECV of age and gender matched HIV- individuals. 53 asymptomatic HIV+ individuals (45 males, median age 48 (IQR:42.5-48) years) on effective cART (CD4+ cell count: 450 cells/μL (IQR: 328-750); plasma HIV RNA: <37 copies/ml in all subjects) and 18 age and gender matched controls (14 males, median age 55 (IQR:44.5-56) years) were retrospectively enrolled. All participants underwent CCT protocol to obtain native and postcontrast Hounsfield unit values of blood and myocardium, ECM was calculated accordingly. The ECV was significantly higher in HIV+ patients than in the control group (ECV: 31% (IQR: 28%-31%) vs 27.4% (IQR: 25%-28%), p<0.001). The duration of cART (standardized=0.56 (0.33-0.95), p=0.014) and the years of exposure to HIV infection [standardized=0.53 (0.4-0.92), p<0.001], were positively and strongly associated with ECV values. Differences in ECV (p<0.001) were also observed regarding the duration of exposure to cART (<5 years, 5-10 years and >10 years). Moreover, ECV was independently associated with age of participants [standardized = 0.42 (0.33-0.89), p=0.084]. We hypothesized that quantitative assessment of tissue ECV would be clinically useful for detecting both focal and diffuse tissue abnormalities in a variety of acute and chronic infectious conditions. ECV imaging can quantitatively characterize tissue inflammation, atypical diffuse fibrosis, and subtle tissue abnormalities not clinically apparent on different method images. Therefore, ECV not only can detect tissue inflammation and/or fibrosis but also might quantify response to treatment during follow-up. HIV infection and exposure to antiretrovirals play a detrimental role on ECV expansion. An increase in ECV indicates ECM expansion, which has been associated to a higher CV risk in the general population. The non-invasive evaluation of ECM trough ECV could represent an important tool to further understand the relationship between HIV infection, cardiac pathophysiology and the increased CV risk observed in PLWH

A feasible and automatic free tool for T1 and ECV mapping

Purpose: Cardiac magnetic resonance (CMR) is a useful non-invasive tool for characterizing tissues and detecting myocardial fibrosis and edema. Estimation of extracellular volume fraction (ECV) using T1 sequences is emerging as an accurate biomarker in cardiac diseases associated with diffuse fibrosis. In this study, automatic software for T1 and ECV map generation consisting of an executable file was developed and validated using phantom and human data. Methods: T1 mapping was performed in phantoms and 30 subjects (22 patients and 8 healthy subjects) on a 1.5T MR scanner using the modified Look-Locker inversion-recovery (MOLLI) sequence prototype before and 15 min after contrast agent administration. T1 maps were generated using a Fast Nonlinear Least Squares algorithm. Myocardial ECV maps were generated using both pre- and post-contrast T1 image registration and automatic extraction of blood relaxation rates. Results: Using our software, pre- and post-contrast T1 maps were obtained in phantoms and healthy subjects resulting in a robust and reliable quantification as compared to reference software. Coregistration of pre- and post-contrast images improved the quality of ECV maps. Mean ECV value in healthy subjects was 24.5% ± 2.5%. Conclusions: This study demonstrated that it is possible to obtain accurate T1 maps and informative ECV maps using our software. Pixel-wise ECV maps obtained with this automatic software made it possible to visualize and evaluate the extent and severity of ECV alterations

Gram-negative septic thrombosis in critically ill patients: A retrospective case-control study

Background: Data on septic thrombosis caused by Gram-negative bacilli (GN-ST) in intensive care unit (ICU) patients are currently limited. Methods: The aim of this retrospective case–control study (matched 1:3) performed over a 15-month period on ICU patients with bacteraemia, associated (cases) or not (controls) with GN-ST, was to assess 30-day mortality and clinical/microbiological features of GN-ST. Results: During the study period, 16 patients with GN-ST and 48 controls were analyzed. Polytrauma was the cause of ICU admission in 12 (75%) cases and 22 (46%) controls (p = 0.019). In no case of septic thrombosis was surgical debridement performed. The site of venous thrombosis was more frequently in the lower limbs, associated with bone fracture in nine out of 12 (75%) cases. The median duration of bacteraemia (22 days vs 1 day; p 72 h was significantly associated with GN-ST (area under the curve (AUC) 0.95, sensitivity 0.996 and specificity 0.810; p < 0.001). Finally, 30-day mortality was 20% in cases and 67% in controls (p < 0.001). Conclusions: Critically ill patients with GN-ST showed specific clinical features. Despite delayed bacteraemia clearance, targeted antibiotic therapy plus anticoagulation usually provided clinical improvement and a low 30-day mortality rate

Diagnostic Value of the Early Heart-to-Mediastinum Count Ratio in Cardiac 123I-mIBG imaging for Parkinson's Disease

Early diagnosis of Parkinson's disease (PD) is of primary importance. The delayed (3-4 h after injection) Iodine-123-Metaiodobenzylguanidine (123I-mIBG) scintigraphy has been proven to be effective in early differential diagnosis for Lewy body disease. But early imaging (15-30 min after injection) has only been marginally studied for its possible diagnostic role. In this prospective study a thresholdfor the early Heart-to-Mediastinum (H/M) count ratio has been investigated, obtaining a diagnostic accuracy analogous to conventional, delayed imaging

A computational tool for evaluating HIFU safety

Background. High Intensity Focused Ultrasound (HIFU) is a noninvasive treatment for therapeutic applications, in particular the treatment of either benign or malignant tumor lesions. HIFU treatment is based on the power of a focused ultrasound beam to locally heat biological tissues over a necrotic level with minimal impact on the surrounding tissues. Therapies based on HIFU are becoming widely spread in the panorama of options offered by the Health Care System. Consequently, there is an ever increasing need to standardise quality assurance protocols and to develop computational tools to evaluate the output of clinical HIFU devices and ensuring safe delivery of HIFU treatment.Aims. Goal of this study is the development of a computational tool for HIFU ablation therapy to assure safety of the patient and effectiveness of the treatment. Results. The simulated results provide information about the behaviour of the focalized ultrasound in their interaction with different biological tissues.Conclusions. Numerical simulation represents a useful approach to predict the heath deposition and, consequently, to assess the safety and effectiveness of HIFU devices

Unexpected increase of myocardial extracellular volume fraction in low cardiovascular risk HIV patients

Background People living with HIV (PLWH) are prone to develop sub-clinical Cardiovascular (CV) disease, despite the effectiveness of combined Antiretroviral Therapy (cART). Algorithms developed to predict CV risk in the general population could be inaccurate when applied to PLWH. Myocardial Extra-Cellular Matrix (ECM) expansion, measured by computed tomography, has been associated with an increased CV vulnerability in HIV-negative population. Measurement of Myocardial Extra-Cellular Volume (ECV) by computed tomography or magnetic resonance, is considered a useful surrogate for clinical evaluation of ECM expansion. In the present study, we aimed to determine the extent of cardiovascular involvement in asymptomatic HIV-infected patients with the use of a comprehensive cardiac computed tomography (CCT) approach. Materials and methods In the present study, ECV in low atherosclerotic CV risk PLWH was compared with ECV of age and gender matched HIV- individuals. 53 asymptomatic HIV + individuals (45 males, age 48 (42.5–48) years) on effective cART (CD4 + cell count: 450 cells/µL (IQR: 328–750); plasma HIV RNA: &lt;37 copies/ml in all subjects) and 18 age and gender matched controls (14 males, age 55 (44.5–56) years) were retrospectively enrolled. All participants underwent CCT protocol to obtain native and postcontrast Hounsfield unit values of blood and myocardium, ECM was calculated accordingly. Results The ECV was significantly higher in HIV + patients than in the control group (ECV: 31% (IQR: 28%-31%) vs. 27.4% (IQR: 25%-28%), p &lt; 0.001). The duration of cART (standardized β = 0.56 (0.33–0.95), p = 0.014) and the years of exposure to HIV infection (standardized β = 0.53 (0.4–0.92), p &lt; 0.001), were positively and strongly associated with ECV values. Differences in ECV (p &lt; 0.001) were also observed regarding the duration of cART exposure (&lt; 5 years, 5–10 years and &gt; 10 years). Moreover, ECV was independently associated with age of participants (standardized β = 0.42 (0.33–0.89), p = 0.084). Conclusions HIV infection and exposure to antiretrovirals play a detrimental role on ECV expansion. An increase in ECV indicates ECM expansion, which has been associated to a higher CV risk in the general population. The non-invasive evaluation of ECM trough ECV could represent an important tool to further understand the relationship between HIV infection, cardiac pathophysiology and the increased CV risk observed in PLWH

Effectiveness of clinical scores in predicting coronary artery disease in familial hypercholesterolemia: a coronary computed tomography angiography study

PurposeOne of the major challenges in the management of familial hypercholesterolemia (FH) is the stratification of cardiovascular risk in asymptomatic subjects. Our purpose is to investigate the performance of clinical scoring systems, Montreal-FH-score (MFHS), SAFEHEART risk (SAFEHEART-RE) and FH risk score (FHRS) equations and Dutch Lipid Clinic Network (DLCN) diagnostic score, in predicting extent and severity of CAD at coronary computed tomography angiography (CCTA) in asymptomatic FH.Material and methodsOne-hundred and thirty-nine asymptomatic FH subjects were prospectively enrolled to perform CCTA. MFHS, FHRS, SAFEHEART-RE and DLCN were assessed for each patient. Atherosclerotic burden scores at CCTA (Agatston score [AS], segment stenosis score [SSS]) and CAD-RADS score were calculated and compared to clinical indices.ResultsNon-obstructive CAD was found in 109 patients, while 30 patients had a CAD-RADS &gt;= 3. Classifying the two groups according to AS, values varied significantly for MFHS (p &lt; 0.001), FHRS (p &lt; 0.001) and SAFEHEART-RE (p = 0.047), while according to SSS only MFHS and FHRS showed significant differences (p &lt; 0.001). MFHS, FHRS and SAFEHEART-RE, but not DLCN, showed significant differences between the two CAD-RADS groups (p &lt; .001).MFHS proved to have the best discriminatory power (AUC = 0.819; 0.703-0.937, p &lt; 0.001) at ROC analysis, followed by FHRS (AUC = 0.795; 0.715-0.875, p &lt; .0001) and SAFEHEART-RE (AUC = .725; .61-.843, p &lt; .001).ConclusionsGreater values of MFHS, FHRS and SAFEHEART-RE are associated to higher risk of obstructive CAD and might help to select asymptomatic patients that should be referred to CCTA for secondary prevention

Oral Bacteriotherapy Reduces the Occurrence of Chronic Fatigue in COVID-19 Patients

Long COVID refers to patients with symptoms as fatigue, “brain fog,” pain, suggesting the chronic involvement of the central nervous system (CNS) in COVID-19. The supplementation with probiotic (OB) would have a positive effect on metabolic homeostasis, negatively impacting the occurrence of symptoms related to the CNS after hospital discharge. On a total of 58 patients hospitalized for COVID-19, 24 (41.4%) received OB during hospitalization (OB+) while 34 (58.6%) taken only the standard treatment (OB–). Serum metabolomic profiling of patients has been performed at both hospital acceptance (T0) and discharge (T1). Six months after discharge, fatigue perceived by participants was assessed by administrating the Fatigue Assessment Scale. 70.7%of participants reported fatigue while 29.3%were negative for such condition. The OB+ group showed a significantly lower proportion of subjects reporting fatigue than the OB– one (p &lt; 0.01). Furthermore, OB+ subjects were characterized by significantly increased concentrations of serum Arginine, Asparagine, Lactate opposite to lower levels of 3-Hydroxyisobutirate than those not treated with probiotics. Our results strongly suggest that in COVID-19, the administration of probiotics during hospitalization may prevent the development of chronic fatigue by impacting key metabolites involved in the utilization of glucose as well as in energy pathways

The role of teicoplanin in the treatment of SARS-CoV-2 infection: a retrospective study in critically ill COVID-19 patients (Tei-COVID Study)

Teicoplanin has a potential antiviral activity expressed against SARS-CoV-2 and was suggested as a complementary option to treat COVID-19 patients. In this multicentric, retrospective, observational research the aim was to evaluate the impact of teicoplanin on the course of COVID-19 in critically ill patients