Immediate flow reserve of Y thoracic artery grafts: an intraoperative flowmetric study

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Repair or prosthesis insertion in ischemic mitral regurgitation: Two faces of the same medal

AbstractObjectiveThe proper treatment of chronic ischemic mitral regurgitation (CIMR) is still under evaluation. The different role of mitral valve repair (MVr) or mitral valve prosthesis insertion (MVPI) is still not defined.MethodsFrom May 2009 to December 2011 167 patients with ejection fraction (EF) ≤ 40% had MV surgery for CIMR, MVr in 135 (80.8%) and MVPI in 32 (19.2%). Indication to MVPI was a MV coaptation depth > 10 mm. EF was lower (26 ± 7 vs 32 ± 6, p = 0.0000) in MVPI, whereas MR grade (3.6 ± 0.8 vs 2.7 ± 0.9, p = 0.0000), left ventricle dimensions (end diastolic, LVEDD, 62 ± 7 vs 57 ± 6 mm, p = 0.0001; end systolic, LVESD, 49 ± 8 vs 44 ± 8 mm, p = 0.0018), systolic pulmonary artery pressure (51 ± 22 vs 41 ± 16 mm Hg, p = 0.0037) and NYHA Class (3.6 ± 0.5 vs 2.8 ± 0.6, p = 0.0000) were higher.ResultsIn-hospital mortality was similar (3.1 vs 3.7%) as well as 3-year survival (86 ± 6 vs 88 ± 4) and survival in NYHA Class I/II (80 ± 5 vs 83 ± 4). One hundred thirty nine patients had an echocardiographic evaluation after a minimum of 4 months (13 ± 8). EF rose significantly in both groups (from 26 ± 7% to 30 ± 4%, p = 0.0122, and from 32 ± 6% to 35 ± 8%, p = 0.0018). LVESD reduced significantly in both groups (from 49 ± 8 to 43 ± 9 mm, p = 0.0109, and from 44 ± 8 to 41 ± 7 mm, p = 0.0033). MR grade was significantly lower in patients who had MVPI (0.1 ± 0.2 vs 0.3 ± 0.3, p = 0.0011).ConclusionsWith appropriate indications, MVPI is a safe procedure which provides similar results to MVr with lower MR return, even if addressed to patients with worse preoperative parameters

Defective One- or Two-electron Reduction of the Anticancer Anthracycline Epirubicin in Human Heart RELATIVE IMPORTANCE OF VESICULAR SEQUESTRATION AND IMPAIRED EFFICIENCY OF ELECTRON ADDITION

One-electron quinone reduction and two-electron carbonyl reduction convert the anticancer anthracycline doxorubicin to reactive oxygen species (ROS) or a secondary alcohol metabolite that contributes to inducing a severe form of cardiotoxicity. The closely related analogue epirubicin induces less cardiotoxicity, but the determinants of its different behavior have not been elucidated. We developed a translational model of the human heart and characterized whether epirubicin exhibited a defective conversion to ROS and secondary alcohol metabolites. Small myocardial samples from cardiac surgery patients were reconstituted in plasma that contained clinically relevant concentrations of doxorubicin or epirubicin. In this model only doxorubicin formed ROS, as detected by fluorescent probes or aconitase inactivation. Experiments with cell-free systems and confocal laser scanning microscopy studies of H9c2 cardiomyocytes suggested that epirubicin could not form ROS because of its protonation-dependent sequestration in cytoplasmic acidic organelles and the consequent limited localization to mitochondrial one-electron quinone reductases. Accordingly, blocking the protonation-sequestration mechanism with the vacuolar H+-ATPase inhibitor bafilomycin A1 relocalized epirubicin to mitochondria and increased its conversion to ROS in human myocardial samples. Epirubicin also formed ∼60% less alcohol metabolites than doxorubicin, but this was caused primarily by its higher Km and lower Vmax values for two-electron carbonyl reduction by aldo/keto-reductases of human cardiac cytosol. Thus, vesicular sequestration and impaired efficiency of electron addition have separate roles in determining a defective bioactivation of epirubicin to ROS or secondary alcohol metabolites in the human heart. These results uncover the molecular determinants of the reduced cardiotoxicity of epirubicin and serve mechanism-based guidelines to improving antitumor therapies

Correlations between the alpha-Gal antigen, antibody response and calcification of cardiac valve bioprostheses: experimental evidence obtained using an alpha-Gal knockout mouse animal model

IntroductionPreformed antibodies against αGal in the human and the presence of αGal antigens on the tissue constituting the commercial bioprosthetic heart valves (BHVs, mainly bovine or porcine pericardium), lead to opsonization of the implanted BHV, leading to deterioration and calcification. Murine subcutaneous implantation of BHVs leaflets has been widely used for testing the efficacy of anti-calcification treatments. Unfortunately, commercial BHVs leaflets implanted into a murine model will not be able to elicit an αGal immune response because such antigen is expressed in the recipient and therefore immunologically tolerated.MethodsThis study evaluates the calcium deposition on commercial BHV using a new humanized murine αGal knockout (KO) animal model. Furtherly, the anti-calcification efficacy of a polyphenol-based treatment was deeply investigated. By using CRISPR/Cas9 approach an αGal KO mouse was created and adopted for the evaluation of the calcific propensity of original and polyphenols treated BHV by subcutaneous implantation. The calcium quantification was carried out by plasma analysis; the immune response evaluation was performed by histology and immunological assays. Anti-αGal antibodies level in KO mice increases at least double after 2 months of implantation of original commercial BHV compared to WT mice, conversely, the polyphenols-based treatment seems to effectively mask the antigen to the KO mice’s immune system.ResultsCommercial leaflets explanted after 1 month from KO mice showed a four-time increased calcium deposition than what was observed on that explanted from WT. Polyphenol treatment prevents calcium deposition by over 99% in both KO and WT animals. The implantation of commercial BHV leaflets significantly stimulates the KO mouse immune system resulting in massive production of anti-Gal antibodies and the exacerbation of the αGal-related calcific effect if compared with the WT mouse. DiscussionThe polyphenol-based treatment applied in this investigation showed an unexpected ability to inhibit the recognition of BHV xenoantigens by circulating antibodies almost completely preventing calcific depositions compared to the untreated counterpart

SAFETY OF REPEATED MDCT WITH CONTRAST COMPOUND IN CASE OF PREVIOUS MILD OR MODERATE ADVERSE REACTION: A SINGLE CENTRE RETROSPECTIVE STUDY.

Adverse reactions to intravenous contrast media (CM) agents are uncommon, although relevant due to the growing number of radiologic examinations that use iodinated contrast agents. We evaluated number and prevalence of adverse contrast reaction using different contrast compound and its natural history in our population, specifically looking to cases of new contrast compound administration was considered clinically necessary

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P < .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients