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(1) Background: Emerging data regarding patients recovered from COVID-19 are reported in the literature, but cardiac sequelae have not yet been clarified. To quickly detect any cardiac involvement at follow-up, the aims of the research were to identify: elements at admission predisposing subclinical myocardial injury at follow up; the relationship between subclinical myocardial injury and multiparametric evaluation at follow-up; and subclinical myocardial injury longitudinal evolution. (2) Methods and Results: A total of 229 consecutive patients hospitalised for moderate to severe COVID-19 pneumonia were initially enrolled, of which 225 were available for follow-up. All patients underwent a first follow-up visit, which included a clinical evaluation, a laboratory test, echocardiography, a six-minute walking test (6MWT), and a pulmonary functional test. Of the 225 patients, 43 (19%) underwent a second follow-up visit. The median time to the first follow-up after discharge was 5 months, and the median time to the second follow-up after discharge was 12 months. Left ventricular global longitudinal strain (LVGLS) and right ventricular free wall strain (RVFWS) were reduced in 36% (n = 81) and 7.2% (n = 16) of the patients, respectively, at first the follow-up visit. LVGLS impairment showed correlations with patients of male gender ( p 0.008, OR 2.32 (95% CI 1.24-4.42)), the presence of at least one cardiovascular risk factor ( p < 0.001, OR 6.44 (95% CI 3.07-14.9)), and final oxygen saturation ( p 0.002, OR 0.99 (95% CI 0.98-1)) for the 6MWTs. Subclinical myocardial dysfunction had not significantly improved at the 12-month follow-ups. (3) Conclusions: in patients recovered from COVID-19 pneumonia, left ventricular subclinical myocardial injury was related to cardiovascular risk factors and appeared stable during follow-up.

Aims: Echocardiography has shown to categorize heart failure (HF) patients according to haemodynamic profiles. Whether left ventricular (LV) global longitudinal strain (LV-GLS) could integrate echo-derived haemodynamic profiles to risk stratify chronic HF patients is still unknown., Methods and Results: Chronic HF outpatients with LV ejection fraction (LV-EF) <50% (n = 351) and LV-GLS assessment were evaluated and divided according to four haemodynamic phenotypes based on LV stroke volume index (SVI), LV filling pressure (LVFP), and right ventricular (RV) function: normal output-normal LVFP (NO-NP), normal output-high LVFP (NO-HP), low output-no RV dysfunction (LO-NRVD), and low output-RV dysfunction (LO-RVD). RV function was defined using the tricuspid annular plane systolic excursion and RV free-wall longitudinal strain. The median follow-up duration was 3.3 years. The combination of all-cause mortality and HF hospitalization was the primary endpoint. Secondary endpoints were all-cause mortality and cardiovascular mortality. The prevalence of NO-NP, NO-HP, LO-NRVD, and LO-RVD were 38%, 22%, 30%, and 10%, respectively. The haemodynamic model independently predicted primary and secondary outcomes, with incremental prognostic information over LV-EF (all P-values <0.001 for C-statistics). When univariate Cox regression analysis was performed to assess the prognostic stratification capability of LV-GLS in different haemodynamic subgroups, we observed a reduction in LV-GLS hazard ratios from the NO-NP to the LO-RVD for every endpoint., Conclusion: There was a continuum in LV-GLS impairment across the spectrum of haemodynamic phenotypes and its prognostic value resulted variable depending on the types of chronic HF patients. The highest prognostic information added by LV-GLS was in patients with normal SVI., Competing Interests: Conflicts of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Recently, questions around the efficacy and effectiveness of Fractional Flow Reserve (FFR) have arisen in various clinical settings., Methods: The Clinical Outcome of FFR-guided Revascularization Strategy of Coronary Lesions (HALE-BOPP) study is an investigator-initiated, multicentre, international prospective study enrolling patients who underwent FFR measurement on at least one vessel. In accordance with the decision-making workflow and treatment, the vessels were classified in three subgroups: (i) angio-revascularized, (ii) FFR-revascularized, (iii) FFR-deferred. The primary endpoint was the occurrence of target vessel failure (TVF, cardiac death, target vessel myocardial infarction and ischemia-driven target vessel revascularization). The analysis was carried out at vessel- and patient-level., Results: 1305 patients with 2422 diseased vessels fulfilled the criteria for the present analysis. Wire-related pitfalls and transient adenosine-related side effects occurred in 0.8% (95% CI: 0.4%-1.4%) and 3.3% (95% CI: 2.5%-4.3%) of cases, respectively. In FFR-deferred vessels, the overall incidence rate of TVF was 0.024 (95% CI: 0.019-0.031) lesion/year. After a median follow-up of 3.6 years, the occurrence of TVF was 6%, 7% and 11.7% in FFR-deferred, FFR-revascularized and angio-revascularized vessels, respectively. Compared to angio-revascularized vessels, FFR-guided vessels (both FFR-revascularized and FFR-deferred vessels) showed a lower TVF incidence rate lesion/year (0.029, 95% CI: 0.024-0.034 vs. 0.049, 95% CI: 0.040-0.061 respectively, p = 0.0001). The result was consistent after correction for confounding factors and across subgroups of clinical interest. The patient-level analysis confirmed the lower occurrence of TVF in negative-FFR vs. positive-FFR subgroups., Conclusions: In a large prospective observational study, an FFR-based strategy for the deferral of coronary lesions is a reliable and safe tool, associated with good outcomes., Clinical Trial Registration: NCT03079739., Competing Interests: SW received speaker fees from Boston Scientific. GC received research grant from Boston Scientific, SMT, Abbott Vascular, Astrazeneca. MT received research grant from GADA, Abbott Vascular. SB received research grant from SMT, Siemens Healthcare, GE Healthcare. Bernardo Cortese and Gianluca Campo are serving as Guest editors of this journal. We declare that Bernardo Cortese and Gianluca Campo had no involvement in the peer review of this article and have no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to Jerome L. Fleg. All other authors have nothing to disclose., (Copyright: © 2023 The Author(s). Published by IMR Press.)

Background: Infective endocarditis (IE) is a significant disease characterized by high mortality and complications. The aim of this study was to evaluate the incidence/100 000 inhabitants and the in-hospital mortality/100 000 inhabitants of IE during the last 10 years in the province of Ravenna., Methods and Results: We reviewed the public hospitals discharge database from January 2010 to December 2020 using the international classification of disease codification (ICD-9) for IE. We used the Italian national statistical institute (ISTAT) archive to estimate the number of Ravenna inhabitants/year. In 10 years, we identified a total of 407 patients with diagnosis of IE.The incidence of IE increased significantly from 6.29 cases/100 000 inhabitants in 2010 to 19.58 cases/100 000 inhabitants in 2020 ( P  < 0.001). Also, the in-hospital mortality from IE increased over the same number of years, from 1.8 deaths/100 000 inhabitants in 2010 to 4.4 deaths/100 000 inhabitants in 2020 ( P  < 0.001). The mortality rate (%) of IE over the years did not increase ( P = 0.565). Also, over the years there was no difference in the site of infection ( P  = 0.372), irrespective of the valve localization or type, native valve ( P  = 0.347) or prosthetic valve ( P  = 0.145). On logistic regression analysis, age was the only predictor of in-hospital mortality (odds ratio 1.045, 95% confidence interval: 1.015; 1.075, P  = 0.003)., Conclusions: Ravenna-based data on IE showed increased disease incidence but unchanged mortality rate over 10 years of follow-up. Age remains the sole predictor of population-based mortality, irrespective of the nature of the valve, native or substitute, and the organism detected on microbiology., (Copyright © 2022 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Background: There is a growing need for studies on ketogenic diet (KD) therapies. Registered dietitian nutritionists (RDNs) should lead efforts to better understand the nutritional risks and benefits of the KD to inform evidence-based practices., Objective: The purpose of this study was to explore participation in research among RDNs practicing in KD therapies for epilepsy and identify barriers to participation., Design: This cross-sectional study collected professional experience, research involvement and output, and perceived barriers to conducting research., Participants/setting: This study surveyed 66 RDNs practicing in KD therapies for epilepsy., Main Outcome Measure: Research involvement was assessed using the Dietitian Research Involvement Survey score. Research output was reported as type and number of publications. Barriers to research included lack of time, resources, administrative support, training, and/or skill., Statistical Analyses: Data were summarized using descriptive statistics, such as means and SDs, medians and interquartile ranges, counts and percentages, as appropriate., Results: The median Dietitian Research Involvement Survey score was 31 out of 60 (range, 16 to 60). Thirty-two participants (48.5%) reported publishing or presenting data, and only 13.6% published an article on ketogenic diet therapies as a leading author. The main barriers to participating in research were insufficient time (83.3%), insufficient funding (81.8%), and priority of work (70.8%). Research involvement scores were not affected by lack of time and resources; however, scores were lower in RDNs reporting lack of interest, training, and skill in research., Conclusions: Although ketogenic RDNs participated in research, most were not leading projects or publications. To increase research involvement among RDNs, focus should include overcoming structural barriers and facilitating knowledge acquisition for those lower on the research continuum., (Copyright © 2022 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the effects of new devices-heat and moisture exchangers (HMEs) and adhesives-on pulmonary symptoms, subject adherence, quality of life, dermatologic symptoms, and patient satisfaction after laryngectomy., Study Design: Prospective crossover study., Setting: Between December 2020 and April 2021, 40 patients were enrolled who had undergone laryngectomy, routinely used HMEs and adhesive, and were followed in our Department of Otolaryngology-Head and Neck Surgery., Methods: Patients were allocated into group A (new products) or group B (usual care) for 6 weeks. Then the 2 groups reversed, and each patient acted as his or her own control. Patients kept a diary and cough tally sheet. At baseline and after each 6-week period, 2 questionnaires were administered: EQ-5D (European Quality of Life-5 Dimensions) and CASA-Q (Cough and Sputum Assessment Questionnaire)., Results: Six weeks of using new products resulted in the following effects for both groups: (1) a significant reduction in daily forced expectoration and dry coughs, (2) a significant improvement in all domains of the CASA-Q, (3) an increase in adherence to HME use, (4) a significant reduction in shortness of breath and skin irritation, and (5) significantly better scores in the anxiety/depression domain of the EQ-5D., Conclusion: Achieving this reduction in patients who were already highly adherent to HME use is clinically relevant and underscores the importance of using better-performing HMEs that can compensate for the humidification deficit. Improving pulmonary symptomatology could reduce patient restrictions in daily life and avoidance of social activity, with a consequent positive effect on quality of life.

Natural killer (NK) cells are emerging as unique players in the immune response against cancer; however, only limited data are available on tumor infiltrating NK cells in head and neck squamous cell carcinoma (HNSCC), one of the most common cancer. Occurrence of HNSCC is closely related to the immune microenvironment, and immunotherapy is increasingly being applied to this setting. However, the limited success of this type of treatment in this tumor calls for further investigation in the field. Surgical HNSSC specimens of 32 consecutive patients were mechanically and enzymatically dissociated. Tumor cells were separated from infiltrating cells by short centrifugation and infiltrating NK cells were phenotypically and functionally characterized by multiple antibody staining and flow cytometry. Tumor infiltrating NK cells in HNSCC showed a peculiar phenotype predominantly characterized by increased NKG2A and reduced Siglec-7, NKG2D, NKp30 and CD16 expression. This phenotype was associated with a decreased ability to perform antibody-dependent cellular cytotoxicity (ADCC). However, NK, CD4 and CD8 shared an increment of glucocorticoid-induced tumor necrosis factor-related (GITR) costimulatory receptor which could be exploited for immunotherapy with agonistic anti-GITR antibodies combined with checkpoint inhibitors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest, (Copyright © 2022 Mele, Pessino, Trisolini, Luchena, Benazzo, Morbini, Mantovani, Oliviero, Mondelli and Varchetta.)

Background: Little evidence to date has described the feasibility and diagnostic accuracy of coronary computed tomography angiography (CCTA) with noninvasive fractional flow reserve (CT-FFR) in coronary vessels with resorbable magnesium scaffold (RMS)., Methods: The SHERPA-MAGIC is a prospective study enrolling patients receiving RMS. The present analysis considered patients undergoing CCTA 18 months after the index procedure. CCTA images were employed to investigate reabsorption status, luminal measurements, and noninvasive FFR. Three-year follow-up was available for all patients., Results: Overall, 26 patients with a total of 29 coronary arteries treated with 35 RMS were considered. The most frequently involved vessel was left anterior descendent (LAD). Median stent length was 25 (20-25) mm, with a median diameter of 3 (3-3.5) mm. At 18-month CCTA, all scaffolded segments were patent. Complete RMS reabsorption was observed in 27 (93%, 95% CI 77-99%) cases. Median minimal lumen diameter (MLD) and area (MLA) of the scaffolded segments were 2.5 [2.1-2.8] mm and 6.4 [4.4-8.4] mm 2 , respectively. Median CT-FFR was 0.88 [0.81-0.91]. Only one (3.5%) vessel showed a flow-limiting CT-FFR value ≤0.80. During the 3-year follow-up, only one (4%) adverse event was observed. Conclusions: In patients undergoing RMS implantation, CCTA including noninvasive CT-FFR evaluation is feasible and allows investigation of long-term RMS performance.

The combined use of Unmanned Aerial Vehicles (UAVs) and Structure from Motion (SfM) photogrammetry allows the collection and processing of high-resolution data on demand, which is key for the constant and detailed monitoring of the fluvial environment. In addition, through the ever-increasing development of new techniques of mapping and data processing (i.e., UAVs swarm, BVLOS flight missions, high-performance photogrammetry workflow), it is now possible to detect large areas at high-resolution, providing support for spatiotemporal insights into hydro-geomorphological processes and hazard assessment, in order to ensure an effective management and to prevent catastrophic phenomena (i.e., floods). The main goal of this paper is to use UAV-based high-resolution topographic data to constrain the probabilistic hazard assessment of extended reaches of Basento river (Basilicata, Italy). To demonstrate the influence of geomorphology and riverbed sediment on hazard assessment, a sensitivity analysis was carried out on the resolution of the UAV-derived DEMs; on the riverbed roughness coefficient resulting from photo-sieving analysis and on the morphological change detection over short-time ranges (2019-2021). We found that lower resolution DEMs lead to an increase of flooding probability (in several river cross-sections an increase even higher than 99 % resulted), and that a greater roughness coefficient involves an increase in the probability of flooding (with a maximum increase of about 9 %). Moreover, the multitemporal high-resolution outputs resulting from SfM allowed the identification of morphological changes, in short-times, caused by an anthropic modification of the river bank, which significantly affected the flooding hazard., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Measures of global left ventricular (LV) systolic function have limitations for the prediction of post-infarct LV remodeling (LVR). Therefore, we tested the association between a new measure of regional LV systolic function—the percentage of severely altered strain (%SAS)- and LVR after acute ST-elevation myocardial infarction (STEMI). As a secondary objective, we also evaluated the association between %SAS and clinical events during follow-up. Methods: Of 177 patients undergoing echocardiography within 24 h from primary percutaneous coronary angioplasty, 172 were studied for 3 months, 167 for 12 months, and 10 died. The %SAS was calculated by dividing the number of LV myocardial segments with ≥−5% peak systolic longitudinal strain by the total number of segments. LVR was defined as the increase in end-diastolic volume >20% at its first occurrence compared to baseline. Results: LVR percentage was 10.2% and 15.8% at 3 and 12 months, respectively. Based on univariable analysis, a number of clinical, laboratory, electrocardiographic and echocardiographic variables were associated with LVR. Based on multivariable analysis, %SAS and TnI peak remained associated with LVR (for %SAS 5% increase, OR 1.226, 95% CI 1.098−1.369, p < 0.0005; for TnI peak, OR 1.025, 95% CI 1.004−1.047, p = 0.022). %SAS and LVR were also associated with occurrence of clinical events at a median follow-up of 43 months (HR 1.02, 95% CI 1.0−1.04, p = 0.0165). Conclusions: In patients treated for acute STEMI, acute %SAS is associated with post-infarct LVR. Therefore, we suggest performing such evaluations on a routine basis to identify, as early as possible, STEMI patients at higher risk.

Background: Natural killer (NK) cells play a key role in immune surveillance and response to tumors, their function regulated by NK cell receptors and their ligands. The DNAM-1 activating receptor recognizes the CD155 molecule expressed in several tumor cells, such as hepatocellular carcinoma (HCC). This study aims to investigate the role of the DNAM-1/CD155 axis in mediating the NK cell response in patients with HCC., Methods: Soluble CD155 was measured by ELISA. CD155 expression was sought in HCC cells by immunohistochemistry, qPCR, and flow cytometry. DNAM-1 modulation in NK cells was evaluated in transwell experiments and by a siRNA-mediated knockdown. NK cell functions were examined by direct DNAM-1 triggering., Results: sCD155 was increased in sera from HCC patients and correlated with the parameters of an advanced disease. The expression of CD155 in HCC showed a positive trend toward better overall survival. DNAM-1 downmodulation was induced by CD155-expressing HCC cells, in agreement with lower DNAM-1 expressions in tumor-infiltrating NK (NK-TIL) cells. DNAM-1-mediated cytotoxicity was defective both in circulating NK cells and in NK-TIL of HCC patients., Conclusions: We provide evidence of alterations in the DNAM-1/CD155 axis in HCC, suggesting a possible mechanism of tumor resistance to innate immune surveillance.

We assessed SARS-CoV-2-specific CD4+ and CD8+ T cell responses in samples from 89 acute COVID-19 patients, utilizing blood samples collected during the first wave of COVID-19 in Italy. The goal of the study was to examine correlations between SARS-CoV-2-specific T cell responses in the early phase comparing mild, moderate, or severe COVID-19 disease outcomes. T cell responses to the spike (S) and non-S proteins were measured in a combined activation-induced marker (AIM) and intracellular cytokine staining (ICS) assay. Early CD4+ T cell responses to SARS-CoV-2 S correlated with milder disease by both AIM and IFNγ ICS readouts. The correlation of S-specific CD4+ T cell responses with milder disease severity was most striking within the first two weeks of symptom onset compared to later time points. Furthermore, donors with milder disease were associated with polyantigenic CD4+ T cell responses that recognized more prominently non-S proteins in addition to S, while severe acute COVID-19 was characterized by lower magnitudes of CD4+ T cell responses and a narrower repertoire. In conclusion, this study highlights that both the magnitude and breadth of early SARS-CoV-2-specific CD4+ T cell responses correlated with milder disease outcomes in acute COVID-19 patients.

Clinical evidence has emphasized the importance of coronary plaques’ characteristics, rather than lumen stenosis, for the outcome of cardiovascular events. Coronary computed tomographic angiography (CCTA) has a well-established role as a non-invasive tool for assessing plaques. The aim of this study was to compare clinical characteristics and CCTA-derived information of stable patients with non-severe plaques in predicting major adverse cardiac events (MACEs) during follow-up. We retrospectively selected 371 patients (64% male) who underwent CCTA in our center from March 2016 to January 2021 with Coronary Artery Disease—Reporting and Data System (CAD-RADS) 0 to 3. Of those, 198 patients (53% male) had CAD-RADS 0 to 1. Among them, 183 (49%) had normal pericoronary fat attenuation index (pFAI), while 15 (60% male) had pFAI ≥ 70.1 Hounsfield unit (HU). The remaining 173 patients (76% male) had CAD-RADS 2 to 3 and were divided into patients with at least one low attenuation plaque (LAP) and patients without LAPs (n-LAP). Compared to n-LAP, patients with LAPs had higher pFAI (p = 0.005) and had more plaques than patients with n-LAP. Presence of LAPs was significantly higher in elderly (p < 0.001), males (p < 0.001) and patients with traditional risk factors (hypertension p = 0.0001, hyperlipemia p = 0.0003, smoking p = 0.0003, diabetes p = <0.0001, familiarity p = 0.0007). Among patients with CAD-RADS 0 to 1, the ones with pFAI ≥ 70.1 HU were more often hyperlipidemic (p = 0.05) and smokers (p = 0.007). Follow-up (25,4 months, range: 17.6−39.2 months) demonstrated that LAP and pFAI ≥ 70.1 significantly and independently (p = 0.04) predisposed to outcomes (overall mortality and interventional procedures). There is an added value of CCTA-derived features in stratifying cardiovascular risk in low- to intermediate-risk patients with non-severe, non-calcified coronary plaques. This is of utmost clinical relevance as it is possible to identify a subset of patients with increased risk who need strengthening in therapeutic management and closer follow-up even in the absence of severe CAD. Further studies are needed to evaluate the effect of medical treatments on pericoronary inflammation and plaque composition.

Background: Although the primary cause of death in COVID-19 infection is respiratory failure, there is evidence that cardiac manifestations may contribute to overall mortality and can even be the primary cause of death. More importantly, it is recognized that COVID-19 is associated with a high incidence of thrombotic complications., Hypothesis: Evaluate if the coronary artery calcium (CAC) score was useful to predict in-hospital (in-H) mortality in patients with COVID-19. Secondary end-points were needed for mechanical ventilation and intensive care unit admission., Methods: Two-hundred eighty-four patients (63, 25 years, 67% male) with proven severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who had a noncontrast chest computed tomography were analyzed for CAC score. Clinical and radiological data were retrieved., Results: Patients with CAC had a higher inflammatory burden at admission (d-dimer, p = .002; C-reactive protein, p = .002; procalcitonin, p = .016) and a higher high-sensitive cardiac troponin I (HScTnI, p = <.001) at admission and at peak. While there was no association with presence of lung consolidation and ground-glass opacities, patients with CAC had higher incidence of bilateral infiltration (p = .043) and higher in-H mortality (p = .048). On the other side, peak HScTnI >200 ng/dl was a better determinant of all outcomes in both univariate (p = <.001) and multivariate analysis (p = <.001)., Conclusion: The main finding of our research is that CAC was positively related to in-H mortality, but it did not completely identify all the population at risk of events in the setting of COVID-19 patients. This raises the possibility that other factors, including the presence of soft, unstable plaques, may have a role in adverse outcomes in SARS-CoV-2 infection., (© 2022 The Authors. Clinical Cardiology published by Wiley Periodicals, LLC.)

Background: HyperDoppler is a new echocardiographic color Doppler-based technique that can assess intracardiac flow dynamics. The aim of this study was to verify the feasibility and reproducibility of this technique in unselected patients and its capability to differentiate measures of vortex flow within the left ventricle (LV) in normal sedentary subjects, athletes, and patients with heart failure. Methods: Two hundred unselected, consecutive patients presenting at the echocardiographic laboratory, 50 normal subjects, 30 athletes, and 50 patients with chronic heart failure and LV ejection fraction <50% were enrolled. Images were acquired using a MyLab X8 echo-scanner. Area, intensity, depth, length, and kinetic energy dissipation (KED) of vortex flow were measured. Results: The HyperDoppler technique feasibility was 94.5%. According to the intraclass correlation coefficient evaluations, repeatability and reproducibility of vortex flow measures were good for vortex area (0.82, 0.85), length (0.83, 0.82), and depth (0.87, 0.84) and excellent for intensity (0.92, 0.90) and KED (0.98, 0.98). Combining different vortex flow measures, the LV flow profile of healthy sedentary individuals, athletes, and heart failure patients could be differentiated. Conclusions: HyperDoppler is a feasible, reliable, and practical technique for the assessment of LV flow dynamics and may distinguish normal subjects and patients with heart failure.

Cardiac involvement has been described during the course of SARS-CoV-2 disease (COVID-19), with different manifestations. Several series have reported only increased cardiac troponin without ventricular dysfunction, others the acute development of left or right ventricular dysfunction, and others myocarditis. Ventricular dysfunction can be of varying degrees and may recover completely in some cases. Generally, conventional echocardiography is used as a first approach to evaluate cardiac dysfunction in patients with COVID-19, but, in some cases, this approach may be silent and more advanced cardiac imaging techniques, such as myocardial strain imaging or cardiac magnetic resonance, are necessary to document alterations in cardiac structure or function. In this review we sought to discuss the information provided by different cardiac imaging techniques in patients with COVID-19, both in the acute phase of the disease and after discharge from hospital, and their diagnostic and prognostic role. We also aimed at verifying whether a specific form of cardiac disease due to the SARS-CoV-2 can be identified.

Aims: The assessment of aortic stenosis (AS) severity is still challenging, especially in abnormal hemodynamic conditions. Left ventricular ejection time (LVET) has been historically related to AS severity, but it also depends on heart rate (HR) and systolic function. Our aim was to verify if correcting LVET (LVET index, LVETI) by its determinants is helpful for the assessment of AS severity, irrespective of hemodynamic conditions. Methods and results: We retrospectively studied 152 patients with AS and 378 patients with heart failure and no-AS. At multivariate analysis, LVET (assessed with pulsed-wave Doppler) showed a strong correlation with stroke volume index (SVI) (Beta 0.354; p < 0.001), HR (−0.385; p < 0.001), AS grade (Beta 0.301; p < 0.001) and, less significantly, ejection fraction (LVEF) (Beta 0.108; p = 0.001). AS grade was confirmed to be a major determinant of LVET, irrespective of forward flow (assessed by SVI and transvalvular flow rate) and LVEF (above and below 50%). A regression equation was derived to index LVET (LVETI) to HR and SVI. By using this formula, LVETI detected severe AS more accurately (AUC 0.812, p < 0.001) than LVET alone (AUC 0.755, p for difference = 0.005). Similar results were observed in patients with abnormal flow status. As an exploratory finding, we observed that the highest tertile of LVETI was associated with a higher rate of aortic valve interventions during follow-up. Conclusions: LVETI correlates with AS severity better than uncorrected LVET, independently from hemodynamic conditions, and may help to discriminate severe AS. This finding needs confirmation in larger prospective multicenter studies.

Thyroid hormones have a considerable influence on cardiac function and structure. There are direct and indirect effects of thyroid hormone on the cardiovascular system, which are prominent in both hypothyroidism and hyperthyroidism. In this review, we discuss how thyroid dysfunction impacts cardiovascular pathophysiology and the underlying molecular mechanisms.

The major histocompatibility complex-class I chain related proteins A and B (MICA/B) is upregulated because of cellular stress and MICA/B shedding by cancer cells causes escape from NKG2D recognition favoring the emergence of cancers. Cholangiocarcinoma (CCA) is a relatively rare, though increasingly prevalent, primary liver cancer characterized by a late clinical presentation and a dismal prognosis. We explored the NKG2D-MICA/B axis in NK cells from 41 patients with intrahepatic cholangiocarcinoma (iCCA). The MICA/B-specific 7C6 mAb was used for ex vivo antibody-dependent cytotoxicity (ADCC) experiments using circulating, non tumor liver- and tumor-infiltrating NK cells against the HuCCT-1 cell line and patient-derived primary iCCA cells as targets. MICA/B were more expressed in iCCA than in non-tumoral tissue, MICA transcription being higher in moderately-differentiated compared with poorly-differentiated cancer. Serum MICA was elevated in iCCA patients in line with higher expression of ADAM10 and ADAM17 that are responsible for proteolytic release of MICA/B from tumor. Addition of 7C6 significantly boosted peripheral, liver- and tumor-infiltrating-NK cell degranulation and IFNγ production toward MICA/B-expressing established cell lines and autologous iCCA patient target cells. Our data show that anti-MICA/B drives NK cell anti-tumor activity, and provide preclinical evidence in support of 7C6 as a potential immunotherapeutic tool for iCCA., Competing Interests: No potential conflicts of interest were disclosed., (© 2022 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Non-invasive Doppler ultrasonographic study of cerebral arteries (transcranial Doppler, TCD) has been extensively applied on both outpatient and inpatient settings. It is performed placing a low-frequency (≤2 MHz) transducer on the scalp of the patient over specific acoustic windows, in order to visualize the intracranial arterial vessels and to evaluate the cerebral blood flow velocity and its alteration in many different conditions. Nowadays a valid indication for TCD in the outpatient setting is the research of right-to-left shunting, responsible for the so-called "paradoxical embolism", most often due to patency of foramen ovale, which is responsible for the majority of cryptogenic strokes occurring in patients younger than 55 years. TCD also allows to classify the grade of severity of such shunts using the so-called "microembolic signal grading score". Therefore, TCD is an essential cardiological exam for the detection of patent foramen ovale, assuming an important role as a first-level examination to guide the subsequent diagnostic-therapeutic management. In addition, TCD has found many useful applications in neurocritical care practice. It is useful for the identification of intracranial vascular stenosis and for the assessment of critical conditions including vasospasm in subarachnoid hemorrhage, traumatic brain injury and brain stem death. It is also used to evaluate cerebral hemodynamic changes after stroke, to investigate cerebral pressure autoregulation, and for the clinical evaluation of cerebral vasomotor reactivity.

Olfactory and taste disorders (OTD) are commonly found as presenting symptoms of SARS-CoV-2 infection in patients with clinically mild COVID-19. Virus-specific T cells are thought to play an important role in the clearance of SARS-CoV-2; therefore the study of T cell specific immune responses in patients with mild symptoms may help to understand their possible role in protection from severe disease. We evaluated SARS-CoV-2-specific T cell responses to four different peptide megapools covering all SARS-CoV-2 proteins during the acute phase of the disease in 33 individuals with mild or no other symptom beside OTD and in 22 age-matched patients with severe infection. A control group of 15 outpatients with OTD and consistently negative nasopharyngeal SARS-CoV-2 RNA swabs and virus-specific IgG serology was included in the study. Increased frequencies of virus-specific CD4 + and CD8 + T cells were found in SARS-CoV-2 positive patients with OTD compared with those with severe COVID-19 and with SARS-CoV-2 negative OTD individuals. Moreover, enhanced CD4 + and CD8 + T-cell activation induced by SARS-CoV-2 peptides was associated with higher interferon (IFN)γ production. Increased frequencies of Spike (S1/S2)-specific CD4 + T cells showing enhanced IFNγ secretion and granzyme B content were associated with serum spike-specific IgG in the OTD group. In conclusion, patients with SARS-CoV-2 induced OTD develop highly functional virus-specific CD4 + and CD8 + T cells during the symptomatic phase of the disease, suggesting that robust and coordinated T-cell responses provide protection against extension of COVID-19 to the lower respiratory tract., Competing Interests: AS is a consultant for Gritstone, Flow Pharma, Arcturus, Immunoscape, 20 CellCarta, OxfordImmunotech and Avalia. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Mele, Calastri, Maiorano, Cerino, Sachs, Oliviero, Mantovani, Baldanti, Bruno, Benazzo, Grifoni, Sette, Mondelli and Varchetta.)

Nuclear imaging plays a pivotal role not only in in the evaluation of myocardial ischemia, but also in the evaluation of cardiac infectious, inflammatory, infiltrative and innervation disorders. Myocardial ischemia and viability, cardiac amyloidosis, sarcoidosis, large vessel vasculitis, infective endocarditis, infected cardiac implantable electronic devices, vascular graft infection, and myocardial innervation dysfunction are the main indications for the use of nuclear medicine procedures in both diagnosis and response assessment. With this summarized paper we share a comprehensive review of the role and the use of nuclear cardiology in different cardiac diseases.

Pyroclastic density currents are ground hugging gas-particle flows associated to explosive volcanic eruptions and moving down a volcano's slope, causing devastation and deaths. Because of the hostile nature they cannot be analyzed directly and most of their fluid dynamic behavior is reconstructed by the deposits left in the geological record, which frequently show peculiar structures such as ripples and dune bedforms. Here, a set of equations is simplified to link flow behavior to particle motion and deposition. This allows to construct a phase diagram by which impact parameters of dilute pyroclastic density currents, representing important factors of hazard, can be calculated by inverting bedforms wavelength and grain size, without the need of more complex models that require extensive work in the laboratory., (© 2021. The Author(s).)

Previous evidence suggests that sialic acid-binding Ig-like lectin 7 (Siglec-7) protein is significantly increased in patients with chronic hepatitis C virus (HCV) infection and directly correlates with clinical parameters of liver inflammation and fibrosis. The aim of this study was to determine the diagnostic value of Siglec-7 as a non-invasive tool to assess liver fibrosis in patients with chronic hepatitis C in a cross-sectional study. Serum levels of Siglec-7 were retrospectively tested in 1007 consecutive patients with chronic HCV infection recruited at three different European sites and data examined by the 'imperfect gold-standard' statistical analysis. Liver stiffness obtained by transient elastography (TE) was considered the standard reference. Liver fibrosis was staged according to published cut-offs of liver stiffness measurement by TE. Accuracy of detection of liver fibrosis stage was not increased by Siglec-7 alone. However, we developed a new index (SiGAP) including Siglec-7, γ-glutamyl transferase, age and platelet count which showed increased sensitivity and specificity in predicting fibrosis compared with APRI or FIB4 indices. The AUROC of SiGAP for the diagnosis of significant (≥F2) and advanced liver fibrosis (≥F3) showed significantly higher values than those of APRI and FIB-4. Siglec-7 may be useful as a complementary tool to assess liver fibrosis stage in patients with chronic hepatitis C when included in a specifically designed algorithm, which showed high level of accuracy in the detection of F2 and F3 fibrosis stage., (© 2021 John Wiley & Sons Ltd.)

Severe mitral regurgitation represents the second most common indication for valve surgery in Europe. In the last decade, transcatheter mitral valve repair has become an established effective and safe treatment option for patients at high or prohibitive operative risk. A relevant proportion of these patients develop significant tricuspid regurgitation. Once considered a benign and reversible finding, nowadays increasing attention is being paid to the coexistence of this valvular disease, as a growing body of evidence points towards its negative prognostic role. Over the last few years, transcatheter repair has been performed successfully also for the treatment of significant tricuspid regurgitation in patients at high surgical risk. Therefore, combined transcatheter repair is emerging as a treatment strategy for high surgical risk patients with both severe mitral and tricuspid regurgitation. In this review, we provide a comprehensive summary of the epidemiology, pathophysiology, and prognostic role of the coexistence of severe mitral and tricuspid regurgitation. We then discuss the evidence in favor of combined surgical treatment and the emerging data supporting combined transcatheter treatment, with attention to available treatment technologies. The paper is further enriched with three practical case reports and with the suggestion of a decision-making algorithm for the management of this complex subset of patients.

In recent years, lung ultrasonography has acquired an important role as a valuable diagnostic tool in clinical practice. The lung is usually poorly explorable, but it provides more acoustic information in pathological conditions that modify the relationship between air, water and tissues. The different acoustic impedance of all these components makes the chest wall a powerful ultrasound reflector: this is responsible for the creation of several artifacts providing valuable information about lung pathophysiology. Lung ultrasonography helps in the diagnostic process of parenchymal and pleural pathologies, in the differential diagnosis of dyspnea and in the clinical and prognostic evaluation of the SARS-CoV-2 infection.

Myocarditis has been reported as a possible clinical presentation or complication in patients with coronavirus disease (COVID)-19 due to SARS-CoV-2. Despite the alarm that this possibility generated among physicians, there is paucity of information about mechanisms, prevalence, prognosis, diagnosis and therapy of myocarditis in the context of COVID-19. This brief review has the goal to revise and summarize current knowledge on myocarditis in COVID-19 patients and underline problems especially related to diagnosis and treatment., (© 2021. Società Italiana di Medicina Interna (SIMI).)

Background: Whereas dependency of left ventricular outflow tract diameter (LVOTD) from body surface area (BSA) has been established and a BSA-based LVOTD formula has been derived, the relationship between LVOTD and aortic root and LV dimensions has never been explored. This may have implications for evaluation of LV output in heart failure (HF) and aortic stenosis (AS) severity., Methods: A cohort of 540 HF patients who underwent transthoracic echocardiography was divided in a derivation and validation subgroup. In the derivation subgroup (N = 340), independent determinants of LVOTD were analyzed to derive a regression equation, which was used for predicting LVOTD in the validation subgroup (N = 200) and compared with the BSA-derived formula., Results: LVOTD determinants in the derivation subgroup were sinuses of Valsalva diameter (SVD, beta = 0.392, P < .001), BSA (beta = 0.229, P < .001), LV end-diastolic diameter (LVEDD, beta = 0.145, P = .001), and height (beta = 0.125, P = .037). The regression equation for predicting LVOTD with the aforementioned variables (LVOTD = 6.209 + [0.201 × SVD] + [1.802 × BSA] + [0.03 × LVEDD] + [0.025 × Height]) did not differ from (P = .937) and was highly correlated with measured LVOTD (R = 0.739, P < .001) in the validation group. Repeated analysis with LV end-diastolic volume instead of LVEDD and/or accounting for gender showed similar results, whereas BSA-derived LVOTD values were different from measured LVOTD (P < .001)., Conclusion: Aortic root and LV dimensions affect LVOTD independently from anthropometric data and are included in a new comprehensive equation for predicting LVOTD. This should improve evaluation of LV output in HF and severity of AS when direct LVOTD measurement is difficult or impossible., (© 2021 Wiley Periodicals LLC.)

Background: Transcatheter ablation is the standasrd treatment for atrioventricular nodal re-entrant tachycardia (AVNRT). However, different techniques are available. Data about the use of irrigated flexible-tip catheters and three-dimensional electroanatomical mapping (3D EAM) for AVNRT ablation are scant. The aim of this study was to evaluate in long-term follow-up efficacy and safety of a novel approach for AVNRT treatment., Methods: This is a cohort single arm study with long-term follow-up. Patients with AVNRT were treated with catheter ablation by means of irrigated flexible-tip catheters combined with 3D EAM., Results: One-hundred-and-fifty patients were enrolled and followed-up for a median of 38 months (minimum 12, maximum 74). Acute procedural success rate was 96.7% (145/150 patients). During follow-up, 11 patients had arrhythmia recurrences (7.3%). No patient developed atrioventricular conduction block with need for pacemaker implantation (0%). Fourteen patients died during follow-up (9.3%)., Conclusions: Acute procedural success and long-term follow-up show that AVNRT could be safely and effectively treated with irrigated flexible-tip catheters and 3D EAM.

Heart failure (HF) is a leading cause of cardiovascular morbidity and mortality. However, its symptoms and signs are not specific or can be absent. In this context, transthoracic echocardiography plays a key role in diagnosing the various forms of HF, guiding therapeutic decision making and monitoring response to therapy. Over the last few decades, new ultrasound modalities have been introduced in the field of echocardiography, aiming at better understanding the morpho-functional abnormalities occurring in cardiovascular diseases. However, they are still struggling to enter daily and routine use. In our review article, we turn the spotlight on some of the newest ultrasound technologies; in particular, analysis of myocardial deformation by speckle tracking echocardiography, and intracardiac flow dynamics by color Doppler flow mapping, highlighting their promising applications to HF diagnosis and management. We also focus on the importance of these imaging modalities in the selection of responses to cardiac resynchronization therapy.

The introduction of high-sensitivity cardiac troponin allowed identifying a proportion of subjects with chest pain and electrocardiographic changes suggestive of myocardial infarction showing <50% coronary artery stenosis. PFAI is a coronary CT marker proved to predict outcome in ischemic heart disease. Based on CMR findings, patients were divided into myocarditis ( n = 15), MINOCA ( n = 14) and TTS ( n = 9) groups. The aim was to estimate the value of pFAI in these groups compared to 12 controls. To evaluate the coronary inflammation "time course," 20 patients underwent CMR and coronary CT scan within 8 days from the onset, the others within 60 days. There were higher values of pFAI in myocarditis (-86.45 HU), MINOCA (-84.63 HU) and TTS (-84.79 HU) compared to controls (-96.02 HU; p = 0.0077). Among patients who underwent CT within 8 days from onset, the MINOCA had a significantly higher pFAI value (-76.91 HU) compared to the control group (-96.02 HU; p = 0.0001). In the group that underwent CT later than 8 days, elevated pFAI values persisted only in the myocarditis and TTS groups, and there was no difference between MINOCA and controls. Our study shows that in patients with a diagnosis of MINOCA, there is acute coronary inflammation, which is more evident within one week from the acute event but tends to disappear with time.

Aims: Right ventricle-pulmonary artery coupling (RVPAC) has emerged from pathophysiology to clinical interest for prognostic implication in heart failure and is commonly measured as the ratio between tricuspid annular plane systolic excursion and systolic pulmonary artery pressure (TAPSE/SPAP). However, feasibility of SPAP is limited (down to 60% in trials, and maybe lower in clinical practice). We ought to assess the prognostic value of the TAPSE times pulmonary acceleration time (TAPSE x pACT) product and TAPSE to peak tricuspid regurgitation velocity (TAPSE/TRV) ratio as new alternative measures of RVPAC., Methods and Results: Two-hundred patients hospitalized with heart failure were followed-up (median time of 2.7 years) and 82 died. Non survivors had significantly lower TAPSE/SPAP, TAPSE x pACT and TAPSE/TRV than survivors (0.31 vs 0.40 mm/mmHg, 130 vs 156 cm·ms, 5.0 vs 5.8 ms, respectively). Four multivariate models were performed, each one including TAPSE, TAPSE/SPAP, TAPSE x pACT or TAPSE/TRV. TAPSE/SPAP resulted the most powerful predictor of mortality (HR 0.74 per mm/mmHg increase, P < 0.001, C-Statistic 0.778), followed by TAPSE x pACT (HR 0.95 per 10 cm·ms increase, P = 0.013, C-Statistic 0.776), TAPSE/TRV (HR 0.76 per ms increase, P < 0.001, C-Statistic 0.774) and TAPSE (HR 0.91 per mm increase, P = 0.003, C-Statistic 0.769). Cutoff values of 140 cm·ms and 5.5 ms were respectively identified for TAPSE x pACT and TAPSE/TRV with receiving operating characteristic analysis for mortality., Conclusion: TAPSE x pACT product and TAPSE/TRV ratio are alternative measures of RVPAC for prognostic assessment in heart failure that can be applied if TAPSE/SPAP is not feasible., Competing Interests: Declaration of Competing Interest Nothing to Disclose., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The great technological advancements in the field of echocardiography have led to applications of stress echocardiography (SE) in almost all diagnostic fields of cardiology, from ischemic heart disease to valvular heart disease and diastolic function. However, the assessment of the right ventricle (RV) in general, and in particular in regard to the contractile reserve of the RV, is an area that has not been previously explored. We, therefore, propose a study to investigate the potential use of SE for the assessment of RV function in adult patients., Aims and Objectives: The primary aim is to evaluate the feasibility of right ventricular SE. The secondary aim is to assess right ventricular contractile reserve., Matherials and Methods: Eighty-one patients undergoing a physical or dobutamine stress echocardiogram for cardiovascular risk stratification or chest pain were the subject of the study. An exercise leg cycle using a standard WHO protocol was used to simultaneously assess the right and left ventricular global and regional function as well as acquiring Doppler data. Whereas the patient had limitations in mobility, a dobutamine SE was be performed. We evaluated the average values of tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC), S-wave, systolic pulmonary artery pressure (sPAP), and right ventricle global longitudinal (free wall) strain (RVGLS) during baseline and at the peak of the effort. RV contractile reserve was defined as the change in RVGLS from rest to peak exercise. We also assessed the reproducibility of these measurements between two different expert operators (blind analysis)., Results: At least 3 over 5 RV function parameters were measurable both during baseline and at the peak of the effort in 95% of patients, while all 5 parameters in 65% of our population, demonstrating an excellent feasibility. All RV-studied variables showed a statistically significant increase ( P < 0.001) at peak compared to the baseline. The average percentage increases at peak were 31.1% for TAPSE, 24.8% for FAC, 50.6% for S-wave, 55.2% for PAPS, and 39.8% for RV strain. The reproducibility between operators at baseline and peak was excellent. Our study demonstrates that TAPSE, FAC, and S-wave are highly feasible at rest and at peak, while TAPSE, S-wave, and sPAP are the most reliable measurements during RV stress echo., Conclusion: RVGLS is useful in the assessment of RV contractile reserve in patients with good acoustic window. Further studies are needed to evaluate the impact of contrast echocardiography in improving RV contractile reserve assessment during SE., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Journal of Cardiovascular Echography.)

Pyroclastic density currents are ground hugging gas-particle flows that originate from the collapse of an eruption column or lava dome. They move away from the volcano at high speed, causing devastation. The impact is generally associated with flow dynamic pressure and temperature. Little emphasis has yet been given to flow duration, although it is emerging that the survival of people engulfed in a current strongly depends on the exposure time. The AD 79 event of Somma-Vesuvius is used here to demonstrate the impact of pyroclastic density currents on humans during an historical eruption. At Herculaneum, at the foot of the volcano, the temperature and strength of the flow were so high that survival was impossible. At Pompeii, in the distal area, we use a new model indicating that the current had low strength and low temperature, which is confirmed by the absence of signs of trauma on corpses. Under such conditions, survival should have been possible if the current lasted a few minutes or less. Instead, our calculations demonstrate a flow duration of 17 min, long enough to make lethal the breathing of ash suspended in the current. We conclude that in distal areas where the mechanical and thermal effects of a pyroclastic density currents are diminished, flow duration is the key for survival.

Non-ST-segment elevation acute coronary syndromes (NSTE-ACSs) are a group of clinical conditions characterized by acute myocardial ischemia. Conventional echocardiography is generally used to evaluate cardiac function using wall motion analysis and left ventricular ejection fraction but may be insufficient to explore all the complex features of NSTE-ACSs, which may vary substantially from patient to patient in terms of severity of ischemia and extent of involved myocardium. In the last years, speckle tracking echocardiography (STE) has become a widely available technique for the non-invasive assessment of cardiac function and has been repeatedly applied in the setting of NSTE-ACSs. In this review we summarize current evidence about the use of STE in patients with NSTE-ACSs, trying to underline advantages and limitations in comparison with conventional echocardiography for: diagnosis of NSTE-ACS, differential diagnosis, identification of high-risk patients, and prediction of outcome., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Survival after cardiac arrest depends on prompt and effective cardiopulmonary resuscitation (CPR). Transesophageal echocardiography (TEE) can be applied to evaluate the effectiveness of chest compression-decompression maneuvers in the setting of cardiac arrest undergoing CPR. The efficacy of chest compression can be continuously assessed by TEE that can improve the effectiveness of CPR guiding the rescuer to optimize or correct chest compression and decompression by directly examining the movements of the cardiac walls and valve leaflets., Purpose: The review describes how to perform TEE in the emergency setting of cardiopulmonary arrest, its advantages, and limitations, and ultimately propose an echo-guided approach to CPR.

The relationship between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and host immunity is poorly understood. We performed an extensive analysis of immune responses in 32 patients with severe COVID-19, some of whom succumbed. A control population of healthy subjects was included. Patients with COVID-19 had an altered distribution of peripheral blood lymphocytes, with an increased proportion of mature natural killer (NK) cells and low T-cell numbers. NK cells and CD8 + T cells overexpressed T-cell immunoglobulin and mucin domain-3 (TIM-3) and CD69. NK cell exhaustion was attested by increased frequencies of programmed cell death protein 1 (PD-1) positive cells and reduced frequencies of natural killer group 2 member D (NKG2D)-, DNAX accessory molecule-1 (DNAM-1)- and sialic acid-binding Ig-like lectin 7 (Siglec-7)-expressing NK cells, associated with a reduced ability to secrete interferon (IFN)γ. Patients with poor outcome showed a contraction of immature CD56 bright and an expansion of mature CD57 + FcεRIγ neg adaptive NK cells compared to survivors. Increased serum levels of IL-6 were also more frequently identified in deceased patients compared to survivors. Of note, monocytes secreted abundant quantities of IL-6, IL-8, and IL-1β which persisted at lower levels several weeks after recovery with concomitant normalization of CD69, PD-1 and TIM-3 expression and restoration of CD8 + T cell numbers. A hyperactivated/exhausted immune response dominate in severe SARS-CoV-2 infection, probably driven by an uncontrolled secretion of inflammatory cytokines by monocytes. These findings unveil a unique immunological profile in COVID-19 patients that will help to design effective stage-specific treatments for this potentially deadly disease.

Ancient Herculaneum papyrus scrolls, hopelessly charred in the 79 A.D. Vesuvius eruption, contain valuable writings of the Greek philosophers of the day, including works of the Epicurean Philodemus. X-ray phase contrast tomography has recently begun unlocking their secrets. However, only small portions of the text hidden inside the scroll have been recover. One of the challenging tasks in Herculaneum papyri investigation is their virtual unfolding because of their highly complicated structure and three-dimensional arrangement. Although this procedure is feasible, problems in segmentation and flattening hinder the unrolling of a large portion of papyrus. We propose a computational platform for the virtual unfolding procedure, and we show the results of its application on two Herculaneum papyrus fragments. This work paves the way to a comprehensive survey and to further interpretation of larger portions of text hidden inside the carbonized Herculaneum papyri.

Background and Aims: Current evidence suggests that dysfunctional natural killer (NK) cell responses during hepatitis C virus (HCV) infection can be restored after viral eradication with direct acting antivirals (DAAs). However, the fate of the recently described adaptive NK cell population, endowed with increased ability to mediate antibody-dependent cell-mediated cytotoxicity (ADCC), during HCV infection is poorly defined, while no study has explored the effects of DAAs on this NK subset., Approach and Results: We performed multicolor flow cytometry to investigate CD57 + FcεRIγ neg adaptive and FcεRIγ pos conventional NK cell phenotype and function before and after DAA treatment in 59 patients chronically infected with HCV, 39 with advanced liver fibrosis, and 20 with mild-moderate liver fibrosis. Moreover, bulk NK cell phenotype and function were analyzed after cytokine activation following contact with K562 target cells. The proportion of FcεRIγ neg NK cells in patients with HCV was associated with increased HCV load at baseline, and it was significantly reduced after treatment. Patients with an advanced fibrosis stage displayed increased NK cell activation and exhaustion markers that normalized after therapy. Of note, adaptive NK cells from patients with HCV were characterized by increased programmed death receptor 1 expression and reduced ADCC activity at baseline. DAA treatment restored ADCC ability and reduced programmed death receptor 1 expression., Conclusions: HCV profoundly affects the frequency, phenotype, and function of adaptive NK cells. DAA therapy restores a normal adaptive NK phenotype and enhances interferon-gamma production by this cell subset., (© 2020 by the American Association for the Study of Liver Diseases.)

Assessment of left ventricular (LV) output in hospitalized patients with heart failure (HF) is important to determine prognosis. Although echocardiographic LV ejection fraction (EF) is generally used to this purpose, its prognostic value is limited. In this investigation LV-EF was compared with other echocardiographic per-beat measures of LV output, including non-indexed stroke volume (SV), SV index (SVI), stroke distance (SD), ejection time (ET), and flow rate (FR), to determine the best predictor of all-cause mortality in patients hospitalized with HF. A final cohort of 350 consecutive patients hospitalized with HF who underwent echocardiography during hospitalization was studied. At a median follow-up of 2.7 years, 163 patients died. Non-survivors at follow-up had lower SD, SVI and SV, but not ET, FR and LV-EF than survivors. At multivariate analysis, only age, systolic blood pressure, chronic kidney disease, chronic obstructive pulmonary disease, use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and SVI remained significantly associated with outcome [HR for SVI 1.13 (1.04-1.22), P = 0.003]. In particular, for each 5 ml/m 2 decrease in SVI, a 13% increase in risk of mortality for any cause was observed. SVI is a powerful prognosticator in HF patients, better than other per-beat measures, which may be simpler but partial or incomplete descriptors of LV output. SVI, therefore, should be considered for the routine echocardiographic evaluation of patients hospitalized with HF to predict prognosis.

Purpose of Review: The aim of this review is to summarily explain what LV synchrony, coordination, myocardial work, and flow dynamics are, trying to clarify their advantages and limitations in the treatment of heart failure patients undergoing or with implanted cardiac resynchronization therapy (CRT)., Recent Findings: CRT is an established treatment for patients with heart failure and left ventricular systolic dysfunction. In the current guidelines, CRT implant indications rely only on electrical dyssynchrony, but in the last years, many aspects of cardiac mechanics (including contractile synchrony, coordination, propagation, and myocardial work) and flow dynamics have been studied using echocardiographic techniques to better characterize patients undergoing or with implanted CRT. However, the concepts, limits, and potential applications of all these echocardiographic evaluations are unclear to most clinicians. The use of left ventricular dyssynchrony and discoordination indices may help to identify those significant mechanical alterations whose correction may increase the probability of a favorable CRT response. Assessment of myocardial work and intracardiac flow dynamics may overcome some limitations of the conventional evaluation of cardiac mechanics but more investigations are needed before extensive clinical application.