Short- and long-term effects of a cardiac rehabilitation program in patients implanted with a left ventricular assist device

The efficacy of cardiac rehabilitation in heart-failure patients who received a left-ventricular assist device (LVAD) instead of heart transplantation (HTx) is still unclear. This study aims to evaluate whether cardiac rehabilitation is beneficial in LVAD as HTx patients in the short term and whether its effects in LVAD patients persist over time. Twenty-five LVAD patients were evaluated by functional and psychological tests at admission (T0) and discharge (T1) of a 4-week inpatient structured rehabilitation program, and follow-ups 3 (T2), 6 (T3), and 12 months (T4) after discharge. Twenty-five matched HTx patients were also studied from T0 to T1 to compare the improvements in the six-minute walk test (6MWT). The quality-of-life scores substantially improved in LVAD patients and the 6MWT showed the same functional recovery as in HTx patients from T0 to T1. After T1, numerous LVAD patients withdrew from the study. However, the 6MWT outcome increased further from T1 to T3, with a positive trend during the follow-ups. Hemoglobin and the ventilatory performance increased, and the psychological perception of heart-failure symptoms and pain further improved at T2. In conclusion, exercise-based rehabilitation programs provide similar beneficial effects in LVAD and HTx patients, without deterioration in LVAD patients up to 12 months after discharge

Psychological disorders after coronary artery by-pass surgery: a one-year prospective study

Background: Coronary artery by-pass surgery (CABG) is often followed by anxiety and depression that require early identification in order to provide adequate psychological support. The predictive role of tests administered soon after CABG on long-term psychological outcomes has been only incompletely explored. Aim, Design and Methods: Aim of this study was to assess post-operative and 12-month persistence of psychological disorders by means of the Minnesota Multiphasic Personality Inventory (MMPI-2) and the depression and state and trait anxiety scales of the Cognitive Behavioural Assessment (CBA-2.0) in 118 male patients admitted to cardiac rehabilitation after CABG. Results: Early after CABG we observed a high prevalence of depression (11.8% by MMPI-2 and 12.7% by CBA) and state anxiety (23.5%). At 1-year the MMPI-2 scale D indicated stable mean score and high scores at entry were predictive of persistent depression. Conversely the CBA-2.0 scale QD score significantly decreased (from 3.86±3.19 to 2.91±3.45, p=0.017). Also ST1 state anxiety significantly decreased (from 35.17±6.95 to 32.55±6.72, p=0.003) whereas ST2 trait anxiety was stable. We found no association between psychometric results and ventricular function, number of grafts or time since diagnosis of coronary artery disease. Conclusions: State anxiety and depression by CBA significantly decreased 1-year after CABG; conversely trait anxiety and depression, investigated by MMPI-2, a more specific personality questionnaire, were stable. High scores for the depression in the scale D of MMPI-2 early after CABG seem to be predictive of the persistence of the disorder at 1-year

Psychological profiles derived by cluster analysis of Minnesota Multiphasic Personality Inventory and long term clinical outcome after coronary artery by pass grafting.

Background: To evaluate the psychological characteristics of coronary heart disease (CHD) patients after coronary artery bypass grafting (CABG) by cluster analysis of Minnesota Multiphasic Personality Inventory (MMPI-2) questionnaires and to assess the impact of the profiles obtained on long-term outcome. Methods: 229 CHD patients admitted to cardiac rehabilitation filled in self-administered MMPI-2 questionnaires early after CABG. We assessed the relation between MMPI- 2 profiles derived by cluster analysis, clinical characteristics and outcome at 3-year follow-up. Results: Among the 215 patients (76% men, median age 66 years) with valid criteria in control scales, we identified 3 clusters (G) with homogenous psychological characteristics: G1 patients (N=75) presented somatoform complaints but overall minimal psychological distress. G2 patients (N=72) presented type D personality traits. G3 subjects (N=68) showed a trend to cynicism, mild increases in anger, social introversion and hostility. Clusters overlapped for clinical characteristics such as smoking (G1 21%, G2 24%, G3 24%, p ns), previous myocardial infarction (G1 43%, G2 47%, G3 49% p ns), LV ejection fraction (G1 60 [51 – 60]; G2 58 [49- 60]; G3 60 [55-60], p ns), 3-vessel-disease prevalence (G1 69%, G2 65%, G3 71%, p ns). Three-year event rates were comparable (G1 15%; G2 18%; G3 15%) and Kaplan- Meier curves overlapped among clusters (p ns). Conclusions: After CABG, the interpretation of MMPI- 2 by cluster analysis is useful for the psychological and personological diagnosis to direct psychological assistance. Conversely, results from cluster analysis of MMPI-2 do not seem helpful to the clinician to predict long term outcome

Antitumor activity of novel POLA1-HDAC11 dual inhibitors

Hybrid molecules targeting simultaneously DNA polymerase α (POLA1) and histone deacetylases (HDACs) were designed and synthesized to exploit a potential synergy of action. Among a library of screened molecules, MIR002 and GEM144 showed antiproliferative activity at nanomolar concentrations on a panel of human solid and haematological cancer cell lines. In vitro functional assays confirmed that these molecules inhibited POLA1 primer extension activity, as well as HDAC11. Molecular docking studies also supported these findings. Mechanistically, MIR002 and GEM144 induced acetylation of p53, activation of p21, G1/S cell cycle arrest, and apoptosis. Oral administration of these inhibitors confirmed their antitumor activity in in vivo models. In human non-small cancer cell (H460) xenografted in nude mice MIR002 at 50 mg/kg, Bid (qd × 5 × 3w) inhibited tumor growth (TGI = 61%). More interestingly, in POLA1 inhibitor resistant cells (H460-R9A), the in vivo combination of MIR002 with cisplatin showed an additive antitumor effect with complete disappearance of tumor masses in two animals at the end of the treatment. Moreover, in two human orthotopic malignant pleural mesothelioma xenografts (MM473 and MM487), oral treatments with MIR002 and GEM144 confirmed their significant antitumor activity (TGI = 72–77%). Consistently with recent results that have shown an inverse correlation between POLA1 expression and type I interferon levels, MIR002 significantly upregulated interferon-α in immunocompetent mice. © 2021 Elsevier Masson SA

Vein wall thickness and severity of pulmonary involvement due to sars n-cov2 virus infection

Background: An observational study involving patients recovered from COVID-19 was conducted in order to evaluate the presence/absence of vein wall thickness increasing, according to the severity of pulmonary involvement quantified with a CT-scoring system. Methods: The venous wall thickness (VWT) of 31 patients (23 males and 8 females) with COVID 19 previously admitted to Federico II University Hospital of Naples was evaluated through ultrasound measurement of the common femoral Vein 1 cm proximal to the saphenous-femoral junction and the popliteal Vein 1 cm distal to the confluence of gemellary veins. Measurements were taken with an automated tool to avoid human error. All patients were evaluated in the supine position. Patients were then stratified into two groups, VWT > 1 mm and VWT 1 mm group was 7.4 (S.D. 4.83), whilst the mean value of the COVID score in the VWT < 1 mm group was 3.82 (S.D 3.34). These findings were determined to be statistically significant in a two-tie Student-T test. The linear regression test between VWT and Covid score values demonstrated a direct relationship between the two variables. Conclusion: These results demonstrate a link between two different aspects of the pathological effects on the vessels during a SARS-COV 2 infection. As such a common primum movens can be hypothesized in both micro-thrombotic and inflammatory processes relating to COVID 19

Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. © 2021, The Author(s)

Psychological profiles derived by cluster analysis of Minnesota Multiphasic Personality Inventory and long term clinical outcome after coronary artery by pass grafting

BACKGROUND: To evaluate the psychological characteristics of coronary heart disease (CHD) patients after coronary artery bypass grafting (CABG) by cluster analysis of Minnesota Multiphasic Personality Inventory (MMPI-2) questionnaires and to assess the impact of the profiles obtained on long-term outcome. METHODS: 229 CHD patients admitted to cardiac rehabilitation filled in self-administered MMPI-2 questionnaires early after CABG. We assessed the relation between MMPI-2 profiles derived by cluster analysis, clinical characteristics and outcome at 3-year follow-up. RESULTS: Among the 215 patients (76% men, median age 66 years) with valid criteria in control scales, we identified 3 clusters (G) with homogenous psychological characteristics: G1 patients (N = 75) presented somatoform complaints but overall minimal psychological distress. G2 patients (N=72) presented type D personality traits. G3 subjects (N=68) showed a trend to cynicism, mild increases in anger, social introversion and hostility. Clusters overlapped for clinical characteristics such as smoking (G1 21%, G2 24%, G3 24%, p ns), previous myocardial infarction (G1 43%, G2 47%, G3 49% p ns), LV ejection fraction (G1 60 [51-60]; G2 58 [49-60]; G3 60 [55-60], p ns), 3-vessel-disease prevalence (G1 69%, G2 65%, G3 71%, p ns). Three-year event rates were comparable (G1 15%; G2 18%; G3 15%) and Kaplan-Meier curves overlapped among clusters (p ns). CONCLUSIONS: After CABG, the interpretation of MMPI-2 by cluster analysis is useful for the psychological and personological diagnosis to direct psychological assistance. Conversely, results from cluster analysis of MMPI-2 do not seem helpful to the clinician to predict long term outcome