New Tricholidic Acid Triterpenoids from the Mushroom Tricholoma ustaloides Collected in an Italian Beech Wood.

The secondary metabolites produced by Tricholoma ustaloides Romagn., a mushroom species belonging to the large Tricholoma genus (Basidiomycota, Tricholomataceae), are unknown. Therefore, encouraged by the interesting results obtained in our previous chemical analyses of a few Tricholoma species collected in Italian woods, we aimed to investigate the secondary metabolites of Tricholoma ustaloides. The chemical analysis involved the isolation and characterization of secondary metabolites through an extensive chromatographic study. The structures of isolated metabolites, including the absolute configuration, were established based on a detailed analysis of MS, NMR spectroscopic, optical rotation, and circular dicroism data, and on comparison with those of related compounds reported in the literature. Two novel lanostane triterpenoids, named tricholidic acids B and C, together with triglycerides, a mixture of free fatty acids, five unidentified metabolites, and the known rare saponaceolides F and J, tricholidic acid, and tricholomenyn C, were isolated from an EtOAc extract of fruiting bodies of Tricholoma ustaloides that were collected in an Italian beech wood. This is the second example of isolation of tricholidic acid derivatives from a natural source. Saponaceolides F and J exhibited high cytotoxicity (IC50 values ≤ 10 µM) against a panel of five human cancer cell lines. The toxicity against myeloid leukemia (HL-60), lung cancer (A-549), hepatocellular cancer (HepG2), renal cancer (Caki-1), and breast cancer (MCF-7) cells was higher than that shown by the very well-known cytotoxic drug cisplatin.

New Tricholomalides D-G from the Mushroom Tricholoma ustaloides Grown in an Italian Beech Wood.

Four novel seconeodolastane diterpenoids, named tricholomalides D-G, were isolated, together with the known tricholomalide C, from the fruiting bodies of Tricholoma ustaloides Romagn., a species belonging to the large Tricholoma genus of higher mushrooms (Basidiomycota, family Tricholomataceae). They were isolated through multiple chromatographic separations, and the structures, including the absolute configuration, were established through a detailed analysis of MS, NMR, and CD spectral data and comparison with related compounds reported in the literature, which has been thoroughly revised.

KRAS: A Druggable Target in Colon Cancer Patients.

Mutations in KRAS are among the most frequent aberrations in cancer, including colon cancer. KRAS direct targeting is daunting due to KRAS protein resistance to small molecule inhibition. Moreover, its elevated affinity to cellular guanosine triphosphate (GTP) has made the design of specific drugs challenging. Indeed, KRAS was considered 'undruggable'. KRASG12C is the most commonly mutated variant of KRAS in non-small cell lung cancer. Currently, the achievements obtained with covalent inhibitors of this variant have given the possibility to assess the best therapeutic approach to KRAS-driven tumors. Mutation-related biochemical assets and the tissue of origin are expected to influence responses to treatment. Further attempts to obtain mutant-specific KRAS (KRASG12C) switch-II covalent inhibitors are ongoing and the results are promising. Drugs targeted to block KRAS effector pathways could be combined with direct KRAS inhibitors, immunotherapy or T cell-targeting approaches in KRAS-mutant tumors. The development of valuable combination regimens will be essential against potential mechanisms of resistance that may arise during treatment.

Sorafenib and hepatocellular carcinoma: is alpha-fetoprotein a biomarker predictive of tumor biology and primary resistance?

Background: Alpha-fetoprotein (AFP) is the only biomarker with proven prognostic value in advanced hepatocellular carcinoma. Preliminary data indicate crosstalk between AFP and VEGF signaling. Methods: The authors looked at 69 patients with advanced hepatocellular carcinoma who were previously tested for VEGFR2 expression, had available baseline AFP serum concentrations and were treated with sorafenib within clinical trials. Results: Shorter progression-free survival and overall survival were associated with increased AFP level and elevated VEGFR2 staining. At multivariate analysis of AFP level was the only independent prognostic factor for progression-free survival and overall survival. Conclusion: The authors' study confirms the adverse prognostic role of elevated baseline AFP and also suggests a possible role of AFP in primary resistance to sorafenib therapy.

Lay abstract Alpha-fetoprotein (AFP) is a plasma protein commonly used as a tumor marker for hepatocellular carcinoma. Sorafenib is a targeted therapy used to block the growth of cancer cells in several ways. It affects various proteins on the surface of cancer cells as well as targets inside the cell. Some of these targets are involved in tumor angiogenesis (growth of new blood vessels). In the present analysis, elevated AFP plasma levels before starting sorafenib therapy were correlated with inferior survival compared with patients with low AFP levels, thus suggesting a possible role of AFP in resistance to sorafenib therapy. Using a specific antibody, the authors also studied the expression on cancer cells of VEGFR2, which is a protein involved in angiogenesis and one of the targets of sorafenib. No correlation was found between AFP level and VEGFR2 expression. The underlying mechanisms involved in resistance to sorafenib therapy still need to be clarified and deserve further studies.

Heterogeneity of Colorectal Cancer Progression: Molecular Gas and Brakes.

The review begins with molecular genetics, which hit the field unveiling the involvement of oncogenes and tumor suppressor genes in the pathogenesis of colorectal cancer (CRC) and uncovering genetic predispositions. Then the notion of molecular phenotypes with different clinical behaviors was introduced and translated in the clinical arena, paving the way to next-generation sequencing that captured previously unrecognized heterogeneity. Among other molecular regulators of CRC progression, the extent of host immune response within the tumor micro-environment has a critical position. Translational sciences deeply investigated the field, accelerating the pace toward clinical transition, due to its strong association with outcomes. While the perturbation of gut homeostasis occurring in inflammatory bowel diseases can fuel carcinogenesis, micronutrients like vitamin D and calcium can act as brakes, and we discuss underlying molecular mechanisms. Among the components of gut microbiota, Fusobacterium nucleatum is over-represented in CRC, and may worsen patient outcome. However, any translational knowledge tracing the multifaceted evolution of CRC should be interpreted according to the prognostic and predictive frame of the TNM-staging system in a perspective of clinical actionability. Eventually, we examine challenges and promises of pharmacological interventions aimed to restrain disease progression at different disease stages.

Prognostic and Predictive Cross-Roads of Microsatellite Instability and Immune Response to Colon Cancer.

Understanding molecular features of colon cancer has shed light on its pathogenesis and progression. Over time, some of these features acquired clinical dignity and were incorporated in decision making. Namely, microsatellite instability (MSI) due to mismatch repair of defects, which primarily was adopted for the diagnosis of Lynch syndrome, became recognized as the biomarker of a different disease type, showing a less aggressive behavior. MSI tumors harbor high amounts of tumor infiltrating lymphocytes (TILs) due to their peculiar load in neoantigens. However, microsatellite stable colon cancer may also show high amounts of TILs, and this feature is as well associated with better outcomes. High TIL loads are in general associated with a favorable prognosis, especially in stage II colon cancer, and therein identifies a patient subset with the lowest probability of relapse. With respect to post-surgical adjuvant treatment, particularly in stage III, TILs predictive ability seems to weaken along with the progression of the disease, being less evident in high risk patients. Moving from cohort studies to the analysis of a series from clinical trials contributed to increase the robustness of TILs as a biomarker. The employment of high TIL densities as an indicator of good prognosis in early-stage colon cancers is strongly advisable, while in late-stage colon cancers the employment as an indicator of good responsiveness to post-surgical therapy requires refinement. It remains to be clarified whether TILs could help in identifying those patients with node-positive cancers to whom adjuvant treatment could be spared, at least in low-risk groups as defined by the TNM staging system.

Tivantinib for second-line treatment of MET-high, advanced hepatocellular carcinoma (METIV-HCC): a final analysis of a phase 3, randomised, placebo-controlled study.

BACKGROUND: Tivantinib (ARQ 197), a selective, oral MET inhibitor, improved overall survival and progression-free survival compared with placebo in a randomised phase 2 study in patients with high MET expression (MET-high) hepatocellular carcinoma previously treated with sorafenib. The aim of this phase 3 study was to confirm the results of the phase 2 trial. METHODS: We did a phase 3, randomised, double-blind, placebo-controlled study in 90 centres in Australia, the Americas, Europe, and New Zealand. Eligible patients were 18 years or older and had unresectable, histologically confirmed, hepatocellular carcinoma, an Eastern Cooperative Oncology Group performance status of 0-1, high MET expression (MET-high; staining intensity score ≥2 in ≥50% of tumour cells), Child-Pugh A cirrhosis, and radiographically-confirmed disease progression after receiving sorafenib-containing systemic therapy. We randomly assigned patients (2:1) in block sizes of three using a computer-generated randomisation sequence to receive oral tivantinib (120 mg twice daily) or placebo (twice daily); patients were stratified by vascular invasion, extrahepatic spread, and α-fetoprotein concentrations (≤200 ng/mL or >200 ng/mL). The primary endpoint was overall survival in the intention-to-treat population. Efficacy analyses were by intention to treat and safety analyses were done in all patients who received any amount of study drug. This study is registered with ClinicalTrials.gov, number NCT01755767. FINDINGS: Between Dec 27, 2012, and Dec 10, 2015, 340 patients were randomly assigned to receive tivantinib (n=226) or placebo (n=114). At a median follow-up of 18·1 months (IQR 14·1-23·1), median overall survival was 8·4 months (95% CI 6·8-10·0) in the tivantinib group and 9·1 months (7·3-10·4) in the placebo group (hazard ratio 0·97; 95% CI 0·75-1·25; p=0·81). Grade 3 or worse treatment-emergent adverse events occurred in 125 (56%) of 225 patients in the tivantinib group and in 63 (55%) of 114 patients in the placebo group, with the most common being ascites (16 [7%] patients]), anaemia (11 [5%] patients), abdominal pain (nine [4%] patients), and neutropenia (nine [4%] patients) in the tivantinib group. 50 (22%) of 226 patients in the tivantinib group and 18 (16%) of 114 patients in the placebo group died within 30 days of the last dose of study medication, and general deterioration (eight [4%] patients) and hepatic failure (four [2%] patients) were the most common causes of death in the tivantinib group. Three (1%) of 225 patients in the tivantinib group died from a treatment-related adverse event (one sepsis, one anaemia and acute renal failure, and one acute coronary syndrome). INTERPRETATION: Tivantinib did not improve overall survival compared with placebo in patients with MET-high advanced hepatocellular carcinoma previously treated with sorafenib. Although this METIV-HCC trial was negative, the study shows the feasibility of doing integral tissue biomarker studies in patients with advanced hepatocellular carcinoma. Additional randomised studies are needed to establish whether MET inhibition could be a potential therapy for some subsets of patients with advanced hepatocellular carcinoma. FUNDING: ArQule Inc and Daiichi Sankyo (Daiichi Sankyo Group).

Expression of pERK and VEGFR-2 in advanced hepatocellular carcinoma and resistance to sorafenib treatment.

BACKGROUND & AIMS: The study aimed to evaluate the tissue expression of molecules involved in intracellular signalling pathways as predictors of response to sorafenib in advanced hepatocellular carcinoma (HCC). METHODS: We considered 77 patients enrolled into three prospective trials of sorafenib treatment for whom pretreatment tumour tissue was available. The tissue expression of ß-catenin, glutamine synthetase (GS), phosphorylated extracellular signal regulated kinase (pERK), phosphorylated v-akt murine thymoma viral oncogene homolog (pAKT) and vascular endothelial growth factor receptor-2 (VEGFR-2) was analysed by immunostaining. Stains were scored semiquantitatively and compared with a reference group of 56 untreated HCCs. RESULTS: Overall, the expression of antigens was comparable between treated and untreated patients. Shorter progression-free survival (PFS) and overall survival (OS) were associated with increased pERK staining (≥ 2+ scores) (PFS: 75th percentile 4.4 vs 8.4 months; P = 0.01; OS: 75th percentile 7.0 vs 15.0 months; P = 0.005) and VEGFR-2 staining (≥ 2+ scores) (PFS: 75th percentile 3.8 vs 7.0 months; P = 0.039; OS: 75th percentile 6.3 vs 15.0 months; P = 0.004). At multivariate analysis, both pERK and VEGFR-2 staining maintained an independent effect on OS (HR 2.09; 95% CI, 1.13-3.86, P = 0.019 and HR 2.28; 95% CI, 1.13-4.61, P = 0.021 respectively). No effect was observed for the other tested biomarkers. CONCLUSIONS: Elevated tissue expression of pERK and VEGFR-2 was predictive of poor outcome in advanced HCC treated with sorafenib.

Genetic abnormalities in adolescents and young adults with neuroblastoma: A report from the Italian Neuroblastoma group.

BACKGROUND: Less than 5% of neuroblastomas (NB) occur in adolescents and young adults (AYA), in whom the disease has an indolent and fatal course. PROCEDURE: We studied the genomic profile and histological characteristics of 34 NBs from AYA patients enrolled in the Italian Neuroblastoma Registry (INBR) between 1979 and 2009. RESULTS: Disease was disseminated in 20 patients and localized in 14; 30/34 tumors were classified as NB and 4/34 as nodular ganglioneuroblastoma (nGNB). Segmental Chromosome Aberrations (SCAs) were observed in 29 tumors (85%) namely 1p imbalance (58%), 17q gain (52%), 9p loss (32%), 11q loss (30%), 1q gain (17%), 7q gain (17%), 2p gain (14%), 3p loss (14%), and 4p loss (7%). MYCN amplification and MYCN gain were detected in 3 (10%) and 2 cases (7%) respectively. An anaplastic lymphoma receptor tyrosine kinase (ALK) gene mutation study on the available cases from this cohort revealed 4/25 (16%) mutated cases. In parallel, alpha thalassaemia/mental retardation syndrome X linked (ATRX) gene mutations were also sought, a novel mutation being detected in 1/21 (4,7%) cases. CONCLUSION: This study confirmed the low incidence of MYCN amplification in AYA and recorded a high frequency of 17q gain and 9p and 11q loss independently from the stage of the disease. The presence of 1q gain, which identifies patients with particularly aggressive disease, relapse and poor survival, was also detected. Furthermore, the frequency of ALK mutations suggests that a target-based therapy with ALK inhibitors might be effective in this subset of patients.

Strong Notch activation hinders bevacizumab efficacy in advanced colorectal cancer.

AIM: To assess the role of Notch activation in predicting bevacizumab efficacy in colorectal cancer (CRC). MATERIALS & METHODS: Notch activation was evaluated by immunohistochemistry (IHC) on 65 CRC enrolled within randomized clinical trials assessing first-line bevacizumab-based chemotherapy and on 21 CRC treated with chemotherapy alone. RESULTS: Strong Notch (IHC 3+) activation was negatively associated with response (18 vs 62% in low Notch cases [IHC 0, 1, 2+]; p = 0.016), progression-free survival (4.9 vs 12.1 months; p = 0.002) and overall survival (19.3 vs 30.4 months; p = 0.039). No correlation was found between Notch activation and clinical outcome in CRC treated with chemotherapy alone. CONCLUSION: A potential role of Notch activation in the antitumor activity of bevacizumab could be hypothesized.

Left atrial enlargement and right ventricular hypertrophy in essential hypertension.

AIM: Diastolic dysfunction related to hypertensive left ventricular hypertrophy (LVH) has been shown to affect right-sided cardiac morphology and haemodynamics. As left atrial enlargement (LAE) is a marker of chronically elevated left ventricular (LV) filling pressure and diastolic dysfunction, we investigated the relationship between LAE and right ventricular hypertrophy (RVH) in systemic hypertension. METHODS: A total of 330 essential hypertensives, categorized according to tertiles of left atrial (LA) diameter indexed to body surface area were considered for the analysis. All subjects underwent a quantitative echocardiographic examination as well as extensive clinical and laboratory investigations. RVH was defined as anterior right ventricular (RV) wall thickness ≥ 6.0/5.5 mm in men and women, respectively, and LVH as LV mass index ≥ 51/47 g/m(2.7) in men and women, respectively. RESULTS: The prevalence of LVH increased across LA diameter tertiles from 21.0% to 50% and that of RVH from 26.3% to 41.8% (p < 0.01for both). This was also the case for biventricular hypertrophy (from 10.0% to 26.0%, p < 0.01). Differences in both LV and RV structure across LA diameter tertiles remained significant after adjusting for age, office systolic/diastolic blood pressure and duration of hypertension. Similar results were obtained when study population was divided according to absolute LA diameter tertiles. CONCLUSIONS: Our findings provide further evidence of an interaction between left and right chambers in systemic hypertension by showing that LAE is associated with RVH. The clinical and prognostic implications of such observation remain be evaluated in future prospective studies.

Left ventricular geometry and diastolic function in the hypertensive heart: impact of age.

BACKGROUND AND AIM: The impact of aging on the relationship between left ventricular (LV) mass/geometry and diastolic function as assessed by updated echocardiographic methods, such as tissue Doppler, is poorly defined. We investigated this issue in a cohort of hypertensive patients. METHODS: A total of 660 hypertensives (mean age 65 ± 13 years, 48% men) with preserved LV systolic function underwent a comprehensive echo-Doppler examination for routine clinical indications. For the present analysis, the subjects have been divided in two age groups (<65 or ≥65 years). RESULTS: Overall, 61% of subjects fulfilled the criteria for LVH, 18% for left atrial (LA) enlargement and 11% for altered LV filling index. Concentric LV geometry was 1.4-fold higher in older hypertensives than in younger counterparts; also the prevalence of LA enlargement and altered LV filling was 2.0- and 1.9-fold higher in the former group, respectively. In older hypertensives, at variance from younger ones, neither LV mass nor relative wall thickness (RWT), a continuous index of LV geometry, were independently correlated to conventional as well as tissue Doppler LV diastolic indexes. CONCLUSIONS: Our findings suggest the relationship between cardiac hypertrophy and diastolic function in hypertensive subjects is affected by aging-associated factors unrelated to the amount of LV mass as assessed by standard echocardiography.

Metabolic syndrome, left ventricular hypertrophy and carotid atherosclerosis in hypertension: a gender-based study.

BACKGROUND: The influence of gender on the association between metabolic syndrome (MS) and subclinical organ damage (OD) has been poorly investigated. The aim of this study was to investigate whether the risk of developing left ventricular hypertrophy (LVH) and carotid atherosclerosis is different in men and women with MS. METHODS: A total of 3752 untreated and treated hypertensive patients (mean age 53.3 ± 12.6, 52.7% men) were considered for this analysis. All patients underwent standard ultrasonographic investigations searching for LVH and carotid atherosclerosis. The MS was defined according to ATP III criteria. RESULTS: LVH was more prevalent in women and men with the MS compared with their counterparts (58% vs 34% and 48% vs 33%, respectively, p < 0.001). This was also the case for carotid plaque prevalence (61% vs 42% and 57% vs 44%, p < 0.001). The prevalence of OD was not different between men and women with MS, after adjusting for confounders. In multivariate analysis, abdominal obesity was the most important MS component independently related to LVH in both genders, followed by blood pressure. As for carotid plaques, blood pressure, hyperglycemia and hypertriglyceridemia turned out to be independent correlates regardless of gender. CONCLUSIONS: Our data indicate that MS is associated with a higher risk of LVH and carotid atherosclerosis irrespective of gender; these findings do not support a gender influence in the association between MS and subclinical OD.

Notch-Jagged1 signaling and response to bevacizumab therapy in advanced colorectal cancer: A glance to radiomics or back to physiopathology?

Introduction: The Notch intracellular domain (NICD) and its ligands Jagged-1(Jag1), Delta-like ligand (DLL-3) and DLL4 play an important role in neoangiogenesis. Previous studies suggest a correlation between the tissue levels of NICD and response to therapy with bevacizumab in colorectal cancer (CRC). Another marker that may predict outcome in CRC is radiomics of liver metastases. The aim of this study was to investigate the expression of NICD and its ligands and the role of radiomics in the selection of treatment-naive metastatic CRC patients receiving bevacizumab. Methods: Immunohistochemistry (IHC) for NICD, Jag1 and E-cadherin was performed on the tissue microarrays (TMAs) of 111 patients with metastatic CRC treated with bevacizumab and chemotherapy. Both the intensity and the percentage of stained cells were evaluated. The absolute number of CD4+ and CD8+ lymphocytes was counted in three different high-power fields and the mean values obtained were used to determine the CD4/CD8 ratio. The positivity of tumor cells to DLL3 and DLL4 was studied. The microvascular density (MVD) was assessed in fifteen cases by counting the microvessels at 20x magnification and expressed as MVD score. Abdominal CT scans were retrieved and imported into a dedicated workstation for radiomic analysis. Manually drawn regions of interest (ROI) allowed the extraction of radiomic features (RFs) from the tumor. Results: A positive association was found between NICD and Jag1 expression (p < 0.001). Median PFS was significantly shorter in patients whose tumors expressed high NICD and Jag1 (6.43 months vs 11.53 months for negative cases; p = 0.001). Those with an MVD score ≥5 (CD31-high, NICD/Jag1 positive) experienced significantly poorer survival. The radiomic model developed to predict short and long-term survival and PFS yielded a ROC-AUC of 0.709; when integrated with clinical and histopathological data, the integrated model improved the predictive score (ROC-AUC of 0.823). Discussion: These results show that high NICD and Jag1 expression are associated with progressive disease and early disease progression to anti VEGF-based therapy; the preliminary radiomic analyses show that the integration of quantitative information with clinical and histological data display the highest performance in predicting the outcome of CRC patients.

Association of left atrial enlargement with left ventricular hypertrophy and diastolic dysfunction: a tissue Doppler study in echocardiographic practice.

BACKGROUND: Left atrial (LA) enlargement is a powerful risk factor for cardiovascular diseases; little information is available about its prevalence and correlates in subjects free of overt cardiac disease seen in echocardiographic practice. AIM: We evaluated the prevalence of LA enlargement (LAE) and the relationship with left ventricular (LV) mass and diastolic function in subjects with preserved LV systolic function referred to an echocardiographic study for routine clinical indications. METHODS: 1104 subjects (mean age 58 ± 16 years, 46% men, 57% hypertensives) underwent a comprehensive echo-Doppler examination. LAE and LV hypertrophy (LVH) were defined as LA volume index (LAVI) >29 ml/m(2) and LV mass index (LVMI) >50 g/h(2.7), respectively. Abnormalities of LV relaxation and LV filling were diagnosed by age-related thresholds of lateral annular velocity (Ei) and by early mitral flow velocity to Ei ratio (E/Ei) ≥16, respectively. RESULTS: Overall, 10% of echocardiographic examinations fulfilled the criteria for LAE, 46% for LVH, 45% for altered LV relaxation and 5% for altered LV filling index. LVH progressively increased from 25% to 75% across LAVI quartiles. More patients in the highest quartile exhibited abnormal indexes of LV relaxation and LV filling compared with lower quartiles. In multivariate analysis, LV mass index (ß = 0.408), age (ß = 0.188), E/Ei ratio (ß = 0.140) and Ei (ß = 0.140) emerged as major correlates of LAE (p at least <0.01 for all). CONCLUSIONS: LAE is a frequent finding in patients with preserved systolic function seen in current practice; this abnormality is strongly related to LVH and to diastolic dysfunction. Early detection of LAE may identify patients at higher cardiovascular risk and promote appropriate prevention strategies.

Age related prevalence of severe left ventricular hypertrophy in essential hypertension: echocardiographic findings from the ETODH study.

AIM: We sought to investigate the prevalence and correlates of severe left ventricular hypertrophy (LVH) in relation to age in a large cohort of essential hypertensives referred to a single outpatient hypertension clinic. METHODS: A total of 3752 (mean age 53±13 years, 53% men) untreated (29.5%) and treated hypertensive patients categorized in three age groups (I: 18-40 years; II: 41-64 years; III: ≥65 years) were considered for this analysis. All patients underwent extensive investigations searching for target organ damage. LVH, defined as LV mass ≥49/45 g/m(2.7) in men/women, respectively, was graded as mild, moderate and severe according to Lang's report. RESULTS: LVH prevalence was 29.4% in group I, 48.2% in group II and 63.6% in group III. Overall, more than one fourth of patients with LVH had a severely increased LV mass index; the likelihood of having severe LVH was two- and four-fold higher in elderly hypertensives than in their middle-aged and young counterparts, respectively. Increasing age and LVH degree were both associated with a greater prevalence of concentric LV geometry as well as of extra-cardiac organ damage (i.e. carotid intima-media thickness). CONCLUSIONS: LVH is a highly prevalent organ damage in essential hypertensives, particularly in the elderly, who exhibited a more severe increase of LV mass index, higher relative wall thickness and extra-cardiac organ damage compared with young and middle-aged sub-groups. Our findings suggest that the assessment of cardiovascular risk by grading LVH rather than simply defining the presence/absence of this cardiac phenotype could improve therapeutic strategies in the hypertensive population, particularly in the elderly.

Effects of the lockdown period on the mental health of elite athletes during the COVID-19 pandemic: a narrative review.

Purpose: This review aimed to assess the effects of COVID-19 pandemic lockdown on mental health to elite athletes. The emotional background influenced their sport career and was examined by questionnaires. Methods: We included original studies that investigated psychological outcomes in elite athletes during COVID-19 lockdown. Sixteen original studies (n = 4475 participants) were analyzed. Results: The findings showed that COVID-19 has an impact on elite athletes' mental health and was linked with stress, anxiety and psychological distress. The magnitude of the impact was associated with athletes' mood state profile, personality and resilience capacity. Conclusion: The lockdown period impacted also elite athletes' mental health and training routines with augmented anxiety but with fewer consequences than the general population thanks to adequate emotion regulation and coping strategies.

Mitral deceleration index is associated with aortic root dilatation and not to biventricular structural changes in essential hypertension.

BACKGROUND AND AIM. The ratio of deceleration time to early mitral wave velocity (mitral deceleration index, MDI) has been recently shown to predict cardiovascular events more precisely than deceleration time alone in human hypertension. Data, however, about the relationship of this parameter with cardiac structure are scant. In the present study, we investigated such an association in uncomplicated essential hypertensives. METHODS. A total of 329 hypertensive subjects categorized in tertiles of MDI were considered for the analysis. All patients underwent the following procedures: (i) physical examination and clinic blood pressure measurement; (ii) routine laboratory investigations; (iii) M-mode, two-dimensional and Doppler echocardiography aimed at a comprehensive assessment of left- and right-sided chambers. RESULTS. Unadjusted left ventricular (LV) mass, right ventricular (RV) and aortic root diameter were significantly higher in the upper MDI tertile, but only aortic root diameter remained significant after adjustment for covariates. A progressive, non-significant increase in biventricular hypertrophy occurred across the MDI tertiles. In a multivariate analysis, MDI was significantly associated with age (ß = 0.229, p = 0.001) and aortic root diameter (ß = 0.226, p = 0.001); this was not the case for deceleration time alone. No association between MDI and LV as well as RV structural parameters was found. CONCLUSION. Our findings indicate that MDI is unrelated to LV and RV structural changes. Altered LV diastolic function, as assessed by MDI but not by deceleration time alone, is independently associated with aortic root dilatation, a phenotype predictive of incident cardiovascular morbidity and mortality.