Polymorphism rs7214723 in CAMKK1: a new genetic variant associated with cardiovascular diseases

Cardiovascular diseases (CVDs) are the leading cause of deaths worldwide. CVDs have a complex etiology due to the several factors underlying its development including environment, lifestyle, and genetics. Given the role of calcium signal transduction in several CVDs, we investigated via PCR-restriction fragment length polymorphism (RFLP) the single nucleotide polymorphism (SNP) rs7214723 within the calcium/calmodulin-dependent kinase kinase 1 (CAMKK1) gene coding for the Ca2+/calmodulin-dependent protein kinase kinase I. The variant rs7214723 causes E375G substitution within the kinase domain of CAMKK1. A cross-sectional study was conducted on 300 cardiac patients. RFLP-PCR technique was applied, and statistical analysis was performed to evaluate genotypic and allelic frequencies and to identify an association between SNP and risk of developing specific CVD. Genotype and allele frequencies for rs7214723 were statistically different between cardiopathic and several European reference populations. A logistic regression analysis adjusted for gender, age, diabetes, hypertension, BMI and previous history of malignancy was applied on cardiopathic genotypic data and no association was found between rs7214723 polymorphism and risk of developing specific coronary artery disease (CAD) and aortic stenosis (AS). These results suggest the potential role of rs7214723 in CVD susceptibility as a possible genetic biomarker

Aldo-keto reductases protect metastatic melanoma from ER stress-independent ferroptosis

The incidence of melanoma is increasing over the years with a still poor prognosis and the lack of a cure able to guarantee an adequate survival of patients. Although the new immuno-based coupled to target therapeutic strategy is encouraging, the appearance of targeted/cross-resistance and/or side effects such as autoimmune disorders could limit its clinical use. Alternative therapeutic strategies are therefore urgently needed to efficiently kill melanoma cells. Ferroptosis induction and execution were evaluated in metastasis-derived wild-type and oncogenic BRAF melanoma cells, and the process responsible for the resistance has been dissected at molecular level. Although efficiently induced in all cells, in an oncogenic BRAF- and ER stress-independent way, most cells were resistant to ferroptosis execution. At molecular level we found that: resistant cells efficiently activate NRF2 which in turn upregulates the early ferroptotic marker CHAC1, in an ER stress-independent manner, and the aldo-keto reductases AKR1C1\u2009\uf7\u20093 which degrades the 12/15-LOX-generated lipid peroxides thus resulting in ferroptotic cell death resistance. However, inhibiting AKRs activity/expression completely resensitizes resistant melanoma cells to ferroptosis execution. Finally, we found that the ferroptotic susceptibility associated with the differentiation of melanoma cells cannot be applied to metastatic-derived cells, due to the EMT-associated gene expression reprogramming process. However, we identified SCL7A11 as a valuable marker to predict the susceptibility of metastatic melanoma cells to ferroptosis. Our results identify the use of pro-ferroptotic drugs coupled to AKRs inhibitors as a new valuable strategy to efficiently kill human skin melanoma cells

Surgical repair of left ventricular free-wall rupture complicating acute myocardial infarction: a single-center 30 years of experience

Background: Left ventricular free-wall rupture (LVFWR) is a catastrophic complication of acute myocardial infarction (AMI). Historically, cardiac surgery is considered the treatment of choice. However, because of the rarity of this entity, little is known regarding the efficacy and safety of surgical treatment for post-infarction LVFWR. The aim of this study was to report a single-center experience in this field over a period of 30 years. Methods: Patients who developed LVFWR following AMI and underwent surgical repair at our Institution from January 1990 to December 2019 were considered. The primary end-point was in-hospital morality rate; secondary outcomes were long-term survival and postoperative complications. Multivariate analysis was carried out by constructing a logistic regression model to identify risk factors for early mortality. Results: A total of 35 patients were enrolled in this study. The mean age was 68.9 years; 65.7% were male. The oozing type of LVFWR was encountered in 29 individuals, and the blowout type in 6 subjects. Sutured repair was used in 77.1% of patients, and sutureless repair in the remaining cases. The in-hospital mortality rate was 28.6%. Low cardiac output syndrome was the main cause of postoperative death. Multivariable analysis identified age >75 years at operation, preoperative cardiac arrest, concurrent ventricular septal rupture (VSR) as independent predictors of in-hospital death. Follow-up was complete in 100% of patients who survived surgery (mean follow-up: 9.3 ± 7.8 years); among the survivors, 16 patients died during the follow-up with a 3-year and 12-year overall survival rate of 82.5% and 55.2%, respectively. Conclusions: Surgical treatment of LVFWR following AMI is possible with acceptable in-hospital mortality and excellent long-term results. Advanced age, concurrent VSR and cardiac arrest at presentation are independent risk factors of poor early outcome

Surgical Repair of Postinfarction Ventricular Septal Rupture: Systematic Review and Meta-Analysis.

Background. Ventricular septal rupture (VSR) is a rare but life-threatening complication after acute myocardial infarction. Although surgical correction is challenging and associated with high mortality, it remains the treatment of choice. This systematic review and meta-analysis aimed to evaluate the early outcome of surgical VSR repair.Methods. We searched electronic databases from January 1998 to February 2020. Studies reporting patients undergoing surgical treatment for VSR were analyzed. The primary outcome assessed was operative mortality. Differences were expressed as odds ratios (ORs) with 95% confidence intervals (CIs) to assess the relationships of predefined surgical variables and clinical prognosis.Results. A total of 6361 adult patients from 41 studies were identified. Operative mortality was 38.2%. Pooled ORs showed increased odds of operative mortality in patients with preoperative or perioperative intraaortic balloon pump insertion (OR = 3.48; 95% CI, 3.01-4.02; P >= .001), right ventricular dysfunction (OR = 2.85; 95% CI, 1.47-5.52; P = .002), posterior VSR (OR = 1.73; 95% CI, 1.30-2.31; P >= .001), and emergency surgery (OR = 3.79; 95% CI, 2.52-5.72; P >= .001). Temporal trend evaluation revealed no difference over time in the operative mortality rate; it was 34% in both time-related groups (1971-2000 versus 2001-2018).Conclusions. Ventricular septal rupture repair has a high operative mortality. Patients with preoperative or perioperative intraaortic balloon pump support, right ventricular dysfunction at presentation, or posterior defects, and those undergoing emergent VSR correction have increased odds of operative mortality. (C) 2021 by The Society of Thoracic Surgeons. Published by Elsevier Inc

A preliminary note on carbon and nitrogen elemental and isotopic composition of Po River suspended load

We present a preliminary note on the carbon and nitrogen elemental and isotopic composition of the suspended load of the Po River, i.e., of the more important river of Italy, sampled in distinct hydrological periods. This paper explains thoroughly the sampling and the employed EA-IRMS analytical method. The results are discussed to (a) discriminate natural (geogenic) and anthropogenic components, (b) delineate geochemical fluxes transferred from the Po River to the Adriatic Sea. The analyses of total carbon (TC between 2.7 and 5.4 wt%; δ13C between −16.1 and −7.5 ‰), properly speciated in its organic (OC between 1.0 and 2.2 wt%; δ13C between −25.1 and −19.7 ‰) and inorganic (IC between 0.9 and 3.5 wt%; δ13C between −0.2 and −3.3 ‰) components are useful to understand the provenance (Alps vs. Apennine) of the particles, whereas the analyses on nitrogen (TN between 0.1 and 0.6 wt%; δ15N between 2.4 and 9.0 ‰) give insights on the pollution affecting the river. The data can be useful to constrain models that investigate the nutrient loads conveyed by the river toward the Adriatic costal ecosystem that is affected by frequent eutrophication processes

Predictive factors of long-term survival in the octogenarian undergoing surgical aortic valve replacement: 12-year single-centre follow-up

The improvement of life expectancy created more surgical candidates with severe symptomatic aortic stenosis and age >80. Therefore, the main objective of this observational, retrospective single-centre study is to compare the long-term survival of octogenarians that have undergone surgical aortic valve replacement (AVR) to the survival of the general population of the same age and to establish whether any perioperative characteristics can anticipate a poor long-term result, limiting the prognostic advantage of the procedure at this age. From 2000 to 2014, 264 octogenarians underwent AVR at our institution. Perioperative data were retrieved from our institutional database and patients were followed up by telephonic interviews. The follow-up ranged between 2 months and 14.9 years (mean 4.1 \ub1 3.1 years) and the completeness was 99.2 %. Logistic multivariate analysis and Cox regression were respectively applied to identify the risk factors of in-hospital mortality and follow-up survival. Our patient population ages ranged between 80 and 88 years. Isolated AVR (I-AVR) was performed in 136 patients (51.5 %) whereas combined AVR (C-AVR) in 128 patients (48.5 %). Elective procedures were 93.1 %. Logistic EuroSCORE was 15.4 \ub1 10.6. In-hospital mortality was 4.5 %. Predictive factors of in-hospital mortality were the non-elective priority of the procedure (OR 5.7, CI 1.28\u201325.7, p = 0.02), cardiopulmonary bypass time (OR 1.02, CI 1.01\u20131.03, p = 0.004) and age (OR 1.36, CI 1.01\u20131.84, p = 0.04). Follow-up survival at 1, 4, 8 and 12 years was 93.4 % \ub1 1.6 %, 72.1 % \ub1 3.3 %, 39.1 % \ub1 4.8 % and 20.1 % \ub1 5.7 %, respectively. The long-term survival of these patients was not statistically different from the survival of an age/gender-matched general population living in the same geographic region (p = 0.52). Predictive factors of poor long-term survival were diabetes mellitus (HR 1.55, CI 1.01\u20132.46, p = 0.05), preoperative creatinine >200 \u3bcmol/L (HR 2.07, CI 1.21\u20133.53, p = 0.007) and preoperative atrial fibrillation (HR 1.79, CI 1.14\u20132.80, p = 0.01). In our experience, AVR can be safely performed in octogenarians. After a successful operation, the survival of these patients returns similar to the general population. Nevertheless, the preoperative presence of major comorbidities such as diabetes mellitus, renal dysfunction and atrial fibrillation significantly impact on long-term results

Safety and Efficacy of Biatrial vs. Left Atrial Surgical Ablation During Concomitant Cardiac Surgery: A Meta-Analysis of Clinical Studies With a Focus on the Causes of Pacemaker Implantation

Introduction: The latest STS guidelines recommend concomitant atrial fibrillation (AF) ablation not only during mitral surgery (Class IA) but also during other\u2010than mitral cardiac surgery procedures (Class IB) in patients with preoperative AF. Conventional Cox\u2010Maze III/IV procedures are performed on both atria (BA), but several studies reported excellent results with left atrial only (LA) ablations: the scope of this study is to compare the safety and efficacy of BA vs LA approach. Methods and Results: Pubmed, Scopus, and WOS were searched from inception to November 2018: 28 studies including 7065 patients and comparing the performance of BA vs LA approaches were identified: of these, 16 (57.1%) enrolled exclusively patients with non\u2010paroxysmal AF forms, 10 (35.7%) focused on mitral surgery as main procedure, and 16 (57.1%) regarded patients undergone Cox\u2010Maze with radiofrequency. The 6\u2010 and 12\u2010months prevalence of sinus rhythm were higher in the BA group (OR, 1.37, CI, 1.09\u20101.73, P = .008 and OR, 1.37, CI, 0.99\u20101.88, P = .05 respectively). Permanent pacemaker (PPM) implantation (OR, 1.85, CI, 1.38\u20102.49,P < .0001) and reopening for bleeding (OR, 1.70, CI, 1.05\u20102.75, P = .03) were higher in the BA group. Among patients undergone PPM implantation, BA group had a significantly higher risk of sinoatrial node dysfunction (OR, 3.01, CI, 1.49\u20106.07,P = .002). Conclusions: Concomitant BA ablation appears superior to LA ablation in terms of efficacy but is associated with a higher risk of bleeding and of PPM implantation, more frequently due to sinoatrial node dysfunction. LA approach should be preferable in patients with a higher risk of bleeding or with perioperative risk factors for PPM implantation

Mechanical Circulatory Support as a Bridge to Definitive Treatment in Post-Infarction Ventricular Septal Rupture

: Ventricular septal rupture (VSR) represents a rare complication of acute myocardial infarction, often presenting with cardiogenic shock and associated with high in-hospital mortality despite prompt intervention. Although immediate surgery is recommended for patients who cannot be effectively stabilized, the ideal timing of intervention remains controversial. Mechanical circulatory support (MCS) may allow hemodynamic stabilization and delay definitive treatment even in critical patients. However, the interactions between MCS and VSR pathophysiology as well as potentially related adverse effects remain unclear. A systematic review was performed, from 2000 onward, to identify reports describing MCS types, effects, complications, and outcomes in the pre-operative VSR-related setting. One hundred eleven studies (2,440 patients) were included. Most patients had well-known negative predictors (e.g., cardiogenic shock, inferior infarction). Almost all patients had intra-aortic balloon pumps, with additional MCS adopted in 129 patients (77.5% being venoarterial extracorporeal membrane oxygenation). Mean MCS bridging time was 6 days (range: 0 to 23 days). In-hospital mortality was 50.4%, with the lowest mortality rate in the extracorporeal membrane oxygenation group (29.2%). MCS may enhance hemodynamic stabilization and delayed VSR treatment. However, the actual effects and interaction of the MCS-VSR association should be carefully assessed to avoid further complications or incorrect MCS-VSR coupling

The effect of timing of cardiac catheterization on acute kidney injury after cardiac surgery is influenced by the type of operation

Background: Acute kidney injury (AKI) is a vexing complication of cardiac surgery. Since exposure to contrast agents is a relevant contributing factor in the development of postoperative AKI, the optimal timing between cardiac catheterization and surgery is decisive. Methods: A total of 2504 consecutive nonemergent patients undergoing isolated coronary artery bypass grafting (CABG), valve surgery (with or without concomitant CABG), and proximal aortic procedures were enrolled. AKI was defined by consensus RIFLE (Risk, Injury, Failure, Loss of function, End-stage renal disease) criteria. The association of postoperative AKI and time between cardiac catheterization and operation was evaluated using multivariable logistic regression modeling and propensity-matched analysis. Results: Postoperative AKI occurred in 230 (9%) patients. The median number of days from cardiac catheterization to operation was 5 (25th to 75th percentile: 2 to 10). The incidence of AKI was significantly higher in patients operated on 641 day after cardiac catheterization compared to those operated on > 1 day after (13% vs. 8%, p = 0.004). The time interval between cardiac catheterization and surgery (tested both as a continuous and a categorical variable) was not an independent AKI predictor in the propensity-matched population or the pre-matched one. Contrast exposure 641 day before surgery was independently associated with postoperative AKI in patients undergoing valve surgery with concomitant CABG only (post-matched: OR 3.68, 95%CI 1.30 to 10.39, p = 0.014). Conclusions: Delaying cardiac surgery beyond 24 h of exposure to contrast agents seems to be justified only in patients undergoing valve surgery with concomitant CABG. \ua9 2014 Elsevier Ireland Ltd. All rights reserved

Mechanical Circulatory Support as a Bridge to Definitive Treatment in Post-Infarction Ventricular Septal Rupture

Ventricular septal rupture (VSR) represents a rare complication of acute myocardial infarction, often presenting with cardiogenic shock and associated with high in-hospital mortality despite prompt intervention. Although immediate surgery is recommended for patients who cannot be effectively stabilized, the ideal timing of intervention remains controversial. Mechanical circulatory support (MCS) may allow hemodynamic stabilization and delay definitive treatment even in critical patients. However, the interactions between MCS and VSR pathophysiology as well as potentially related adverse effects remain unclear. A systematic review was performed, from 2000 onward, to identify reports describing MCS types, effects, complications, and outcomes in the pre-operative VSR-related setting. One hundred eleven studies (2,440 patients) were included. Most patients had well-known negative predictors (e.g., cardiogenic shock, inferior infarction). Almost all patients had intra-aortic balloon pumps, with additional MCS adopted in 129 patients (77.5% being venoarterial extracorporeal membrane oxygenation). Mean MCS bridging time was 6 days (range: 0 to 23 days). Inhospital mortality was 50.4%, with the lowest mortality rate in the extracorporeal membrane oxygenation group (29.2%). MCS may enhance hemodynamic stabilization and delayed VSR treatment. However, the actual effects and interaction of the MCS-VSR association should be carefully assessed to avoid further complications or incorrect MCS-VSR coupling. (C) 2021 by the American College of Cardiology Foundation