The evolving role of interventional cytopathology from thyroid FNA to NGS: Lessons learned at Federico II University of Naples.

Fine-needle aspiration (FNA) guided by ultrasound (US) has emerged as a highly precise diagnostic method for managing thyroid nodules, significantly diminishing unnecessary surgeries. The effectiveness of US-guided FNA is high when a single specialist performs the FNA procedure and the microscopy. This paradigm has paved the way for the evolution of interventional cytopathology, a specialist with a pivotal role in the preoperative diagnostic process, encompassing patient history review, clinical examination, FNA execution under US guidance, preparation, and microscopic interpretation of cytological samples. As the landscape of precision medicine unfolds, molecular testing assumes greater importance in thyroid cytopathology, particularly in refining the risk of malignancy for indeterminate nodules. The updated Bethesda classification system underscores the clinical significance of molecular tests, emphasizing their role in refining diagnostic accuracy. With this evolving landscape, interventional cytopathologists must adapt by acquiring expertise in molecular technologies and addressing ongoing challenges in workflow harmonization and optimization. This paper delves into our decade-long experience as interventional cytopathologists, focusing on recent endeavours to ensure adequate samples not only for microscopic diagnosis but also for molecular testing. Additionally, here we review the challenges of integrating next-generation sequencing (NGS) technology into clinical practice, highlighting the importance of integrating clinically meaningful molecular data into comprehensive molecular cytology reports.

HBV Infection and Host Interactions: The Role in Viral Persistence and Oncogenesis.

Hepatitis B virus (HBV) is a major cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Despite the advent of vaccines and potent antiviral agents able to suppress viral replication, recovery from chronic HBV infection is still an extremely difficult goal to achieve. Complex interactions between virus and host are responsible for HBV persistence and the risk of oncogenesis. Through multiple pathways, HBV is able to silence both innate and adaptive immunological responses and become out of control. Furthermore, the integration of the viral genome into that of the host and the production of covalently closed circular DNA (cccDNA) represent reservoirs of viral persistence and account for the difficult eradication of the infection. An adequate knowledge of the virus-host interaction mechanisms responsible for viral persistence and the risk of hepatocarcinogenesis is necessary for the development of functional cures for chronic HBV infection. The purpose of this review is, therefore, to analyze how interactions between HBV and host concur in the mechanisms of infection, persistence, and oncogenesis and what are the implications and the therapeutic perspectives that follow.

Remdesivir Plus Dexamethasone Versus Dexamethasone Alone for the Treatment of Coronavirus Disease 2019 (COVID-19) Patients Requiring Supplemental O2 Therapy: A Prospective Controlled Nonrandomized Study.

BACKGROUND: Remdesivir is an antiviral used to treat coronavirus disease 2019 (COVID-19), which improves some clinical outcomes. Dexamethasone has been shown to be effective in reducing mortality. It has been hypothesized that combination of these two drugs can improve mortality. We evaluated the effect of combination on mortality of COVID-19 patients requiring O2 therapy. METHODS: A prospective quasi-experimental study, including two independent, sequential controlled cohorts, one received remdesivir-dexamethasone and the other dexamethasone alone, was designed. All COVID-19 patients requiring supplemental O2 therapy were enrolled consecutively. The sample size to power mortality was a priori calculated. The primary endpoints were 30-day mortality and viral clearance differences. Secondary endpoints were differences in hospitalization times, improvement in respiratory failure (PO2/FiO2) and inflammatory indices (fibrinogen, CRP, neutrophil/lymphocyte ratio, D-Dimer). Kaplan-Meier curves and the log-rank test were used to evaluate significant differences in mortality between groups. RESULTS: In total, 151 COVID-19 patients were enrolled (remdesivir/dexamethasone group, 76, and dexamethasone alone, 75). No differences in demographic, clinical, and laboratory characteristics were observed between the 2 groups at baseline. Faster viral clearance occurred in the remdesivir/dexamethasone group compared to dexamethasone alone (median 6 vs 16 days; P < .001). The 30-day mortality in the remdesivir/dexamethasone group was 1.3%, whereas in dexamethasone alone was 16% (P < .005). In the remdesivir/dexamethasone group compared to dexamethasone alone there was a reduction in hospitalization days (P < .0001) and a faster improvement in both respiratory function and inflammatory markers. CONCLUSIONS: Remdesivir/dexamethasone treatment is associated with significant reduction in mortality, length of hospitalization, and faster SARS-CoV-2 clearance, compared to dexamethasone alone.

Non-invasive respiratory support in SARS-CoV-2 related acute respiratory distress syndrome: when is it most appropriate to start treatment?

BACKGROUND: Acute respiratory distress syndrome (ARDS) is one of the most severe complications of SARS-CoV-2 infection. Non-Invasive Respiratory Support (NRS) as Continuous Positive Airway Pressure (CPAP) and/or Non-Invasive Ventilation (NIV) has been proven as effective in the management of SARS-CoV-2-related ARDS. However, the most appropriate timing for start NRS is unknown. METHODS: We conducted a prospective pilot study including all consecutive patients who developed moderate SARS-CoV-2-related ARDS during hospitalization. Patients were randomly divided into two intervention groups according to ARDS severity (assessed by PaO2/FiO2-P/F) at NRS beginning: group A started CPAP/NIV when P/F was ≤ 200 and group B started CPAP/NIV when P/F was ≤ 150. Eligible patients who did not give their consent to CPAP/NIV until the severe stage of ARDS and started non-invasive treatment when P/F ≤ 100 (group C) was added. The considered outcomes were in-hospital mortality, oro-tracheal intubation (OTI) and days of hospitalization. RESULTS: Among 146 eligible patients, 29 underwent CPAP/NIV when P/F was ≤ 200 (Group A), 68 when P/F was ≤ 150 (Group B) and 31 patients agreed to non-invasive treatment only when P/F was ≤ 100 (Group C). Starting NRS at P/F level between 151 and 200 did not results in significant differences in the outcomes as compared to treatment starting with P/F ranging 101-150. Conversely, patients undergone CPAP/NIV in a moderate stage (P/F 101-200) had a significantly lower in-hospital mortality rate (13.4 vs. 29.0%, p = 0.044) and hospitalization length (14 vs. 15 days, p = 0.038) than those in the severe stage (P/F ≤ 100). Age and need for continuous ventilation were independent predictors of CPAP/NIV failure. CONCLUSIONS: Starting CPAP/NIV in patients with SARS-CoV-2-related ARDS in moderate stage (100 > P/F ≤ 200) is associated to a reduction of both in-hospital mortality and hospitalization length compared to the severe stage (P/F ≤ 100). Starting CPAP/NIV with a P/F > 150 does not appear to be of clinical utility.

PNPLA3 I148M Polymorphism Influences Renal Function in Children With Obesity and Prediabetes.

OBJECTIVE: Nonalcoholic fatty liver disease negatively impacts on renal function with the contribution of the I148 M variant in the patatin-like phospholipase-containing domain 3 (PNPLA3) gene. We hypothesized that children with prediabetes present with a lower estimated glomerular filtration rate (eGFR) than those with normal glucose tolerance (NGT) and that the 148M PNPLA3 allele could play a worsening role. We aimed evaluating the influence of the I148 M PNPLA3 polymorphism on the relationship between the eGFR and prediabetes in children with obesity. METHODS: One thousand thirty-six children underwent to complete assessment and were genotyped for the I148 M PNPLA3 polymorphism. RESULTS: Patients with prediabetes showed lower eGFR levels (171.03 ± 40.32 vs. 190.80 ± 41.71 mL/min/1.73 m2; P = .001) and higher prevalence of nonalcoholic fatty liver disease (80% vs. 59%; P = .003) than those with NGT. Children with prediabetes showed lower eGFR levels than those with NGT (150.97 ± 14.56 vs. 192.88 ± 40.09; P < .0001) among carriers of the PNPLA3 148M allele. This was not confirmed among patients homozygous for the PNPLA3 I148 allele. A general linear model for eGFR variance confirmed an inverse and significant association of the eGFR with prediabetes in patients carrying the 148M PNPLA3 allele but not in patients homozygous for the PNPLA3 I148 allele. CONCLUSIONS: Prediabetes negatively affects renal function in children with obesity. This effect is heightened in patients carrying the PNPLA3 148M allele.

Pediatric obesity-related non-alcoholic fatty liver disease: waist-to-height ratio best anthropometrical predictor.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder in pediatric obesity. Our study aims to identify a predictive anthropometrical measure for NAFLD in obese children. METHODS: We retrospectively enrolled children and adolescents with obesity. Physical, biochemical, and ultrasound assessments were available. ROC curve tests were performed to identify the best predictor of NAFLD among waist-to-height ratio (WHR), BMI z-score, and triponderal mass index (TMI, an anthropometric index recently associated with increased adiposity in children). Subsequently, a cut-off value was identified. RESULTS: In total, 1900 children and adolescents (1011 with NAFLD) were included. WHR (AUC 0.62, 95% CI 0.59-0.64) was the best predictor of NAFLD compared to BMI z-score (AUC 0.58, 95% CI 0.55-0.60) and TMI (AUC 0.58, 95% CI 0.55-0.61). WHR ≥ 0.53 in boys and 0.63 in girls displayed the best sensitivity and specificity for NAFLD presence. In addition, children with high WHR showed a significantly higher risk of NAFLD (boys: OR 2.43, 95% CI 1.61-3.68, p < 0.0001; girls: OR 1.92, 95% CI 1.58-2.34, p < 0.0001) and elevated ALT (OR 5.71, 95% CI 2.09-15.56, p = 0.0007; girls: OR 2.16, 95% CI 1.70-2.74, p < 0.0001) independent of covariates. CONCLUSIONS: WHR might represent a good anthropometric tool to candidate children and adolescents to NAFLD screening. WHR cut-off differs according to sex, being lower in boys than girls. IMPACT: Waist-to-height ratio is a better predictor of non-alcoholic fatty liver disease risk compared to other anthropometric measures in obese children and adolescents. The predictive cut-off of waist-to-height ratio differs between boys and girls, being lower in boys than girls. The use of waist-to-height ratio measurement and its cut-off in clinical practice might help clinician in identifying obese children and adolescents at risk of non-alcoholic fatty liver disease.

Long-term improvement in cardiac magnetic resonance in ß-thalassemia major patients treated with deferasirox extends to patients with abnormal baseline cardiac function.

The management of iron overload in thalassemia has changed dramatically since the implementation of magnetic resonance imaging, which allows detection of preclinical iron overload and prevention of clinical complications. This study evaluated the effect of deferasirox (DFX), the newest once-daily oral chelator, on cardiac function, iron overload and cardiovascular events over a longer follow up in a "real world" setting. Longitudinal changes in cardiac magnetic resonance T2*, cardiac function parameters and cardiovascular clinical events were assessed in a cohort of 98 TM patients exposed to DFX for a mean of 6.9 years (range 1.8-11.6 years). No cardiac death or incident heart failure occurred. Cardiac T2* significantly increased (+2.6 ± 11.9 msec; P = 0.035) in the whole population, with a significantly greater increase (+11.6 ± 15.5 msec, P = 0.019) in patients with cardiac iron overload (T2* <20 ms). A significant improvement in left-ventricular ejection fraction (LVEF) (from 50.6 ± 6 to 60.2 ± 5; P = 0.001) was observed in 11 (84.6%) out of 13 patients who normalized cardiac function (LVEF >56%). Arrhythmias were the most frequent cardiac adverse event noted but none led to DFX discontinuation. Our data indicate that DFX is effective in maintaining cardiac iron level in the normal range and in improving cardiac iron overload. No heart failure or cardiac death was reported over this longer observation up to 12 years. For the first time, a DFX-induced improvement in LVEF was observed in a subgroup of patients with abnormal cardiac function at baseline, a preliminary observation which deserves further evaluation.

Advances in Pharmacological Approaches for Managing Hypercholesterolemia: A Comprehensive Overview of Novel Treatments.

Hypercholesterolemia plays a crucial role in the formation of lipid plaques, particularly with elevated low-density lipoprotein (LDL-C) levels, which are linked to increased risks of cardiovascular disease, cerebrovascular disease, and peripheral arterial disease. Controlling blood cholesterol values, specifically reducing LDL-C, is widely recognized as a key modifiable risk factor for decreasing the morbidity and mortality associated with cardiovascular diseases. Historically, statins, by inhibiting the enzyme ß-hydroxy ß-methylglutaryl-coenzyme A (HMG)-CoA reductase, have been among the most effective drugs. However, newer non-statin agents have since been introduced into hypercholesterolemia therapy, providing a viable alternative with a favorable cost-benefit ratio. This paper aims to delve into the latest therapies, shedding light on their mechanisms of action and therapeutic benefits.

Left bundle branch pacing and cardiac remodeling in HF patients with type 2 diabetes mellitus: epigenetic pathways and clinical outcomes.

Background: Left bundle branch (LBB) pacing could achieve cardiac resynchronization therapy (CRT) in patients who cannot be resynchronized via the placement of the left ventricle (LV) lead into the coronary sinus. LBB pacing could improve cardiovascular outcomes in heart failure (HF) patients with LBB block who are affected by type 2 diabetes mellitus (T2DM). Study hypothesis: LBB pacing could increase the number of CRT responders and lead to the best clinical outcomes in HF patients with T2DM, inducing cardiac remodeling and improving left ventricle ejection fraction (LVEF) via microRNA (miR) modulation. Methods: In a multicenter observational study, we enrolled 334 HF patients with LBB block and an indication to receive LBB pacing for CRT. In these patients, we evaluated the CRT responder rate, clinical outcomes, and miR expression at 1 year of follow-up. Results: At 1 year of follow-up, we had 223 responders (66.8%), 132 hospitalizations for HF (39.5%), 24 cardiac deaths (7.2%), and 37 all-cause deaths (11.1%), with a higher rate of HF hospitalizations (77 (69.4%) vs 55 (24.7%), p < 0.05), and cardiac deaths (13 (11.7% vs 11 (4.9%), p < 0.05) in non-responders vs responders. At the end of follow-up, we found the lowest expression of miR-26, miR-29, miR-30, miR-92, and miR-145 in LBB-pacing non-responders vs responders (p < 0.05), and a direct correlation between miR-30 (0.340, [0.833-1.915]; p 0.001), the 6-minute-walking test (6MWT; 0.168, [0.008-0.060]; p 0.011), angiotensin-receptor-neprilysin inhibitors (ARNI; 0.157, [0.183-4.877]; p 0.035), sodium-glucose-transporter-2 inhibitors (0.245, [2.242-7.283]; p 0.001), and LVEF improvements. C reactive protein (CRP) inversely correlated with LVEF improvement (-0.220, [-(0.066-0.263)]; p 0.001). ARNI (1.373, CI 95% [1.007-1.872], p 0.045), miR-30 (2.713, CI 95% [1.543-4.769], p 0.001), and 6MWT (1.288, CI 95% [1.084-1.998], p 0.001) were predictors of LBB pacing responders at 1 year of follow-up. Conclusion: LBB-pacing responders evidenced miR modulation, which was linked to significant improvement of the cardiac pump. Specifically, miR-30 was linked to cardiac pump improvement and predicted responders at 1 year of follow-up in patients with T2DM.

Novel cAMP binding protein-BP (CREBBP) mutation in a girl with Rubinstein-Taybi syndrome, GH deficiency, Arnold Chiari malformation and pituitary hypoplasia.

BACKGROUND: Rubinstein-Taybi syndrome (RTS) is a rare autosomal dominant disorder (prevalence 1:125,000) characterised by broad thumbs and halluces, facial dysmorphism, psychomotor development delay, skeletal defects, abnormalities in the posterior fossa and short stature. The known genetic causes are point mutations or deletions of the cAMP-response element binding protein-BP (CREBBP) (50-60% of the cases) and of the homologous gene E1A-binding protein (EP300) (5%). CASE PRESENTATION: We describe, for the first time in literature, a RTS Caucasian girl, 14-year-old, with growth hormone (GH) deficiency, pituitary hypoplasia, Arnold Chiari malformation type 1, double syringomyelic cavity and a novel CREBBP mutation (c.3546insCC). CONCLUSION: We hypothesize that CREBBP mutation we have identified in this patient could be responsible also for RTS atypical features as GH deficiency and pituitary hypoplasia.

Sodium-Glucose Co-Transporters Family: Current Evidence, Clinical Applications and Perspectives.

Sodium-glucose co-transporters (SGLTs) family members are involved in several vital biological functions. Except for SGLT3, they are involved in the mechanisms of active transport of sodium and glucose and several micromolecules. The discovery of functions and mechanisms of SGLT1 inhibition and, in particular, of SGLT2 has radically changed the natural history of some pathologies. SGLT2 inhibitors have revolutionized the therapeutic approach not only of type 2 diabetes mellitus but also of heart failure and chronic kidney failure. Considering the role played by the other SGLTs and the functions still unknown to date, clinical implications of the inhibition of SGLT2 could represent the prelude for a wider modulation of these cotransporters. A better understanding of the role and function of SGLTs could represent a revolution in the therapeutic approach in the hepatological, metabolic, neurological and oncological fields. The purpose of this review is to illustrate the knowledge currently available on SGLTs, its clinical implications and future perspectives.

Predictors of early and late hepatocellular carcinoma recurrence.

Hepatocellular carcinoma (HCC) is the most frequent liver neoplasm, and its incidence rates are constantly increasing. Despite the availability of potentially curative treatments (liver transplantation, surgical resection, thermal ablation), long-term outcomes are affected by a high recurrence rate (up to 70% of cases 5 years after treatment). HCC recurrence within 2 years of treatment is defined as "early" and is generally caused by the occult intrahepatic spread of the primary neoplasm and related to the tumor burden. A recurrence that occurs after 2 years of treatment is defined as "late" and is related to de novo HCC, independent of the primary neoplasm. Early HCC recurrence has a significantly poorer prognosis and outcome than late recurrence. Different pathogenesis corresponds to different predictors of the risk of early or late recurrence. An adequate knowledge of predictive factors and recurrence risk stratification guides the therapeutic strategy and post-treatment surveillance. Patients at high risk of HCC recurrence should be referred to treatments with the lowest recurrence rate and when standardized to combined or adjuvant therapy regimens. This review aimed to expose the recurrence predictors and examine the differences between predictors of early and late recurrence.

Long-Term Prognosis among COVID-19 Patients: The Predictive Role Played by Hyperinflammation and Arrhythmic Disorders in Fatal Outcome.

Limited data are available on outcomes among COVID-19 patients beyond the acute phase of the disease. All-cause mortality among our COVID-19 patients one year after hospital discharge and factors/conditions associated with death were evaluated. All patients discharged from our COVID center were periodically evaluated by clinical assessment and by digital healthcare registry consultation. All findings acquired on discharge day represented the baseline data and were utilized for statistics. Of the 208 patients admitted, 187 patients were discharged. Among these, 17 patients died within 12 months (non-survivors). Compared to survivors, non-survivor patients were significantly (p < 0.05) older, exhibited significantly greater comorbidities and prevalence of active malignancy, heart failure, and arrhythmias, and showed significantly higher circulating levels of B-type natriuretic peptide, troponin, C-reactive protein, and d-dimer, as well as a longer heart-rate-corrected QT interval and significantly lower values for the glomerular filtration rate. Following multivariate analysis, cancer, arrhythmias, and high C-reactive protein levels were found to be factors independently associated with death. At the one-year follow-up, about 9% of patients discharged from our COVID center had a fatal outcome. Ageing, myocardial injury, impaired renal function, and, in particular, cancer, hyperinflammation, and arrhythmias represented strong predictors of the worst long-term outcome among COVID-19 patients.

Liver Involvement during SARS-CoV-2 Infection Is Associated with a Worse Respiratory Outcome in COVID-19 Patients.

Coronavirus disease of 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may be complicated by life-threatening interstitial pneumonia. SARS-CoV-2 infection may also damage several tissues and/or organs beyond the lungs, including the liver. However, controversy still exists as to whether SARS-CoV-2-induced liver alterations can have an impact on the outcome of COVID-19. The aim of this study was therefore to assess whether SARS-CoV-2-infected patients with liver abnormalities at the time of hospital referral had a worse outcome with respect to patients with no liver biochemistry alterations. To this end, the medical records of 123 patients admitted to our COVID center between the end of 2020 and spring 2021 were retrospectively reviewed. Patients were divided into two groups: those with normal liver biochemistries (group 1, 77 patients) and those with altered liver function tests (group 2, 46 patients). Serum levels of aminotransferases (AST and ALT) and bile duct cell injury markers (γ-GT and ALP) were used to dichotomize patients. A higher percentage of patients with liver enzyme alterations were found to develop COVID-19 pneumonia with respect to group 1 patients (74% vs. 65%); moreover, they needed more days of respiratory support and, more importantly, more intensive administration of supplemental oxygen. A statistically significant correlation was also found between aminotransferase levels and duration of respiratory support. The mortality rate was not superior in group 2 vs. group 1 patients. In conclusion, liver abnormalities on admission predisposed COVID-19 patients to development of more severe interstitial pneumonia, because of a longer requirement for supplemental oxygen and a more intensive respiratory support, indicative of a worse disease evolution in these patients.

Gender Differences in the Pathogenesis and Risk Factors of Hepatocellular Carcinoma.

Several chronic liver diseases are characterized by a clear gender disparity. Among them, hepatocellular carcinoma (HCC) shows significantly higher incidence rates in men than in women. The different epidemiological distribution of risk factors for liver disease and HCC only partially accounts for these gender differences. In fact, the liver is an organ with recognized sexual dysmorphism and is extremely sensitive to the action of androgens and estrogens. Sex hormones act by modulating the risk of developing HCC and influencing its aggressiveness, response to treatments, and prognosis. Furthermore, androgens and estrogens are able to modulate the action of other factors and cofactors of liver damage (e.g., chronic HBV infection, obesity), significantly influencing their carcinogenic power. The purpose of this review is to examine the factors related to the different gender distribution in the incidence of HCC as well as the pathophysiological mechanisms involved, with particular reference to the central role played by sex hormones.

Mortality and risk factors of vaccinated and unvaccinated frail patients with COVID-19 treated with anti-SARS-CoV-2 monoclonal antibodies: A real-world study.

OBJECTIVES: There is a scarcity of data on the outcomes and predictors of therapeutic failure of monoclonal antibodies (mAbs) in frail patients with COVID-19. METHODS: Prospective study including consecutive COVID-19 outpatients referred by primary care physicians for mAb treatment. The outcomes evaluated were 60-day mortality, time to SARS-CoV-2 clearance, need for hospitalization, and O2 therapy. RESULTS: Among 1026 COVID-19 patients enrolled, 60.2% received casirivamab/imdevimab and 39.8% sotrivimab. Median age was 63 years, 52.4% were males and median time from positive nasopharyngeal swab to mAbs administration was 3 days (interquartile range, 2-5). 78.1% were vaccinated. Overall, the 60-day mortality was 2.14%. No differences in outcomes were observed between the two mAbs used. No difference was observed in mortality between vaccinated and unvaccinated patients (P = 0.925); although, lower rate of hospitalization (P <0.005), less need for O2 therapy (P <0.0001) and reduced nasopharyngeal swab negativity time (P <0.0001) were observed in vaccinated patients. Early administration of mAbs was associated with lower mortality (P <0.007), whereas corticosteroid use worsened prognosis (P <0.004). The independent predictors associated with higher mortality were older age (P <0.0001), presence of active hematologic malignancies (P <0.0001), renal failure (P <0.041), and need for O2 therapy (P <0.001). CONCLUSION: This study shows similar effectiveness among mAbs used, regardless of vaccination status and identifies patients with COVID-19 in whom mAbs have poor activity.

Cardiac-derived extracellular matrix: A decellularization protocol for heart regeneration.

Extracellular matrix (ECM) is a fundamental component of the heart, guiding vital cellular processes during organ homeostasis. Most cardiovascular diseases lead to a remarkable remodeling of the ECM, accompanied by the formation of a fibrotic tissue that heavily compromises the heart function. Effective therapies for managing fibrosis and promoting physiological ECM repair are not yet available. The production of a decellularized extracellular matrix (d-ECM) serving as a three-dimensional and bioactive scaffold able to modulate cellular behavior and activities is considered crucial to achieve a successful regeneration. The protocol represents a step-by-step method to obtain a decellularized cardiac matrix through the combination of sodium dodecyl sulphate (SDS) and Triton X-100. Briefly, cardiac samples obtained from left ventricles of explanted, pathological human hearts were dissected and washed to remove residual body fluids. Samples were then snap-frozen and sliced by a cryostat into 350 µm thick sections. The sections obtained were decellularized using a solution containing 1% Triton X-100 and 1% SDS in combination, for 24 hours, until observing the color change from brownish-red to translucent-white. As a result, the protocol shows efficiency in preserving ECM architecture and protein composition during the whole process, suggesting that it is worthwhile, highly reproducible and produces a well- preserved decellularized extracellular matrix from cardiac samples. Notwithstanding, some limitations need to be addressed, such as the risk for microbial contamination and the unpredictable trend of the protocol when applied to decellularize samples other than myocardium, vessels, or skin. These issues require antibiotics mixture supplement during the procedure followed by UV sterilization, and appropriate adjustments for a tissue-specific utilization, respectively. The protocol is intended to produce a cardiac d-ECM for cell settlement, representing the ideal scaffold for tissue engineering purposes.

Human Cardiac Progenitor Cell-Derived Extracellular Vesicles Exhibit Promising Potential for Supporting Cardiac Repair in Vitro.

Although human Cardiac Progenitor Cells (hCPCs) are not retained by host myocardium they still improve cardiac function when injected into ischemic heart. Emerging evidence supports the hypothesis that hCPC beneficial effects are induced by paracrine action on resident cells. Extracellular vesicles (EVs) are an intriguing mechanism of cell communication based on the transport and transfer of peptides, lipids, and nucleic acids that have the potential to modulate signaling pathways, cell growth, migration, and proliferation of recipient cells. We hypothesize that EVs are involved in the paracrine effects elicited by hCPCs and held accountable for the response of the infarcted myocardium to hCPC-based cell therapy. To test this theory, we collected EVs released by hCPCs isolated from healthy myocardium and evaluated the effects they elicited when administered to resident hCPC and cardiac fibroblasts (CFs) isolated from patients with post-ischemic end-stage heart failure. Evidence emerging from our study indicated that hCPC-derived EVs impacted upon proliferation and survival of hCPCs residing in the ischemic heart and regulated the synthesis and deposition of extracellular-matrix by CFs. These findings suggest that beneficial effects exerted by hCPC injection are, at least to some extent, ascribable to the delivery of signals conveyed by EVs.

COVID-19 and arrhythmia: The factors associated and the role of myocardial electrical impulse propagation. An observational study based on cardiac telemetric monitoring.

Background: The heart is commonly involved in COVID-19, and rhythm disorders have been largely reported. Objective: To evaluate the association of some non-cardiac and cardiac comorbidities and QT dispersion with arrhythmias and their impact on outcomes in hospitalized patients with COVID-19. Methods: Each patient underwent cardiac telemetry monitoring through the entire hospitalization period, laboratory analyses, 12-lead ECG, and lung imaging examination. Patients with arrhythmia were divided into three groups (bradyarrhythmias, tachyarrhythmias, and tachy- and bradyarrhythmias). Results: Two-hundred patients completed the study (males, 123; mean age, 70.1 years); of these, 80 patients (40%) exhibited rhythm disorders on telemetry. Patients with arrhythmia were older (p < 0.0001), had a greater number of comorbidities (p < 0.0001), higher values of creatinine (p = 0.007), B-type natriuretic peptide (p < 0.0001), troponin (p < 0.0001), C-reactive protein (p = 0.01), ferritin (p = 0.001), D-dimer (p < 0.0001), procalcitonin (p = 0.0008), QT interval (p = 0.002), QTc interval (p = 0.04), and QTc dispersion (p = 0.01), and lower values of sodium (p = 0.03), magnesium (p = 0.04), glomerular filtration rate (p < 0.0001), and hemoglobin (p = 0.008) as compared to patients without arrhythmia. By comparing the three subgroups of patients, no significant differences were found. At multivariate analysis, age [odds ratio (OR) = 1.14 (95% CI: 1.07-1.22); p = 0.0004], coronary artery disease [OR = 12.7 (95% CI: 2.38-68.01); p = 0.005], and circulating troponin [OR = 1.05 (95% CI: 1.003-1.10); p = 0.04] represented risk factors independently associated with arrhythmia. All-cause in-hospital mortality was ∼40-fold higher among patients with arrhythmia [OR = 39.66 (95% CI: 5.20-302.51); p = 0.0004]. Conclusion: Arrhythmias are associated with aging, coronary artery disease, subtle myocardial injury, hyperinflammatory status, coagulative unbalance, and prolonged QTc dispersion in patients with COVID-19, and confer a worse in-hospital prognosis. Given its usefulness, routinary use of cardiac telemetry should be encouraged in COVID wards.

Prediction of SARS-CoV-2-Related Lung Inflammation Spreading by V:ERITAS (Vanvitelli Early Recognition of Inflamed Thoracic Areas Spreading).

Background Coronavirus disease 2019 (COVID-19) can be complicated by interstitial pneumonia, possibly leading to severe acute respiratory failure and death. Because of variable evolution ranging from asymptomatic cases to the need for invasive ventilation, COVID-19 outcomes cannot be precisely predicted on admission. The aim of this study was to provide a simple tool able to predict the outcome of COVID-19 pneumonia on admission to a low-intensity ward in order to better plan management strategies for these patients. Methods The clinical records of 123 eligible patients were reviewed. The following variables were analyzed on admission: chest computed tomography severity score (CTSS), PaO2/FiO2 ratio, lactate dehydrogenase (LDH), neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio, C-reactive protein (CRP), fibrinogen, D-dimer, aspartate aminotransferase (AST), alanine aminotransferase, alkaline phosphatase, and albumin. The main outcome was the intensity of respiratory support (RS). To simplify the statistical analysis, patients were split into two main groups: those requiring no or low/moderate oxygen support (group 1); and those needing subintensive/intensive RS up to mechanical ventilation (group 2). Results The RS intensity was significantly associated with higher CTSS and NLR scores; lower PaO2/FiO2 ratios; and higher serum levels of LDH, CRP, D-dimer, and AST. After multivariate logistic regression and ROC curve analysis, CTSS and LDH were shown to be the best predictors of respiratory function worsening. Conclusions Two easy-to-obtain parameters (CTSS and LDH) were able to reliably predict a worse evolution of COVID-19 pneumonia with values of >7 and >328 U/L, respectively.