Heart rate score in remote monitoring: An additional tool for predicting outcomes in heart failure with reduced ejection fraction.

BACKGROUND: Heart rate score (HRS) ≥ 70% has been associated with arrhythmic events and mortality but these studies were not specific for heart failure (HF) patients. We hypothesized that HRS ≥ 70% obtained from remote monitoring (RM) is associated with HF hospitalizations and arrhythmic events in HF with reduced ejection fraction (HFrEF). METHODS: HRS was calculated from RM in patients with HFrEF and ICD or CRT-D. Two groups were defined: HRS ≥ 70% (G1, n = 55) and HRS < 70% (G2, n = 48) RESULTS: A total of 103 patients were included (64.4 ± 13.04 years, 69.9% male, mean left ventricular ejection fraction (LVEF) 33.62 ± 11.97% and FUP 61.7 ± 38.87 months). The device was CRT-D in 59.2% and ICD in 40.8% and the majority (90.3%) had the device implanted in primary prevention. G1 patients were more frequently male (p = .017) and had more coronary disease (p = .035). HRS ≥70% was an independent predictor for unplanned HF hospitalizations (OR: 1.905 (95% CI: 1.328-3.649), p < .001)). The indication for device implantation (primary vs. secondary prevention), type of device, NYHA class, age, gender and LVEF were not independent predictors of the outcome. VF (4.9 ± 20.0 G1 vs. 1.1 ± 5.47 G2, p = .046) and VT episodes were more prevalent in G1 (3.1 ± 8.93 G1 vs. 0.3 ± 1.59 G2, p = .026), as well as appropriate device shocks (4.3 ± 12.06 G1 vs. 0.3 ± 1.49 G2, p = .023). There was no difference in inappropriate shocks or mortality outcomes between groups. CONCLUSION: HRS ≥70% obtained from RM was an independent predictor of HF hospitalizations and was associated with arrhythmic events with VT and VF episodes and appropriate device shocks in HFrEF patients.

Chronic constrictive pericarditis: a rare cardiac involvement in primary Sjögren's syndrome.

BACKGROUND: Constrictive pericarditis represents a chronic condition and systemic inflammatory diseases are a known, yet uncommon, cause. Pericardial involvement is seldom reported in primary Sjögren's syndrome, usually occurring in association with pericardial effusion or pericarditis. We report a case of constrictive pericarditis with an insidious course and unusual evolution associated with primary Sjögren's syndrome. Due to the challenging nature of the diagnosis, clinical suspicion and multimodality imaging are essential for early identification and prompt initiation of treatment. Long-term outcomes remain uncertain. To the best of our knowledge, no other cases linking this autoimmune disease to constrictive pericarditis have been reported. CASE PRESENTATION: We present the case of a 48-year-old male patient with moderate alcohol habits and a history of two prior hospitalizations. On the first, the patient was diagnosed with primary Sjögren's syndrome after presenting with pleural effusion and ascites, and empirical corticosteroid regiment was initiated. On the second, two-years later, he was readmitted with complaints of dyspnea and abdominal distension. Thoracic computed tomography revealed a localized pericardial thickening and a thin pericardial effusion, both of which were attributed to his rheumatic disease. A liver biopsy showed hepatic peliosis, which was considered to be a consequence of glucocorticoid therapy. Diuretic therapy was adjusted to symptom-relief, and a tapering corticosteroid regimen was adopted. Four years after the initial diagnosis, the patient was admitted again with recurrent dyspnea, orthopnea and ascites. At this time, constrictive pericarditis was diagnosed and a partial pericardiectomy was performed. Although not completely asymptomatic, the patient reported clinical improvement since the surgery, but still with a need for baseline diuretic therapy. CONCLUSION: Albeit uncommon, connective tissue disorders, such as primary Sjögren's syndrome, should be considered as a potential cause of constrictive pericarditis, especially in young patients with no other classical risk factors for constriction. In this case, after excluding possible infectious, neoplastic and autoimmune conditions, a primary Sjögren´s syndrome in association with constrictive pericarditis was assumed. This case presents an interesting and challenging clinical scenario, highlighting the importance of clinical awareness and the use of multimodal cardiac imaging for early recognition and treatment.

Contact allergy to a subcutaneous implantable cardiac defibrillator - A rare problem with a golden solution.

Contact allergy to implantable cardiac defibrillators (ICD) is an uncommon and underdiagnosed complication. We report a case of a 20-years-old man patient that was resuscitated from sudden cardiac death. Workup imaging study was unremarkable, but genetic testing identified a mutation in the KCNH2 gene of uncertain significance. The patient underwent a subcutaneous implantable cardiac defibrillator (S-ICD) implantation, with no complications. The patient suffered two hospital re-admissions due to a device-related inflammatory reaction, leading to two device re-implantations. At the first time, it was considered a bacterial infection and the S-ICD was replaced by an endovascular device. At the second time, a tissue-device interaction, with hypersensitivity reaction and device rejection was suspected. The skin patch-tests were inconclusive, but it was decided to implant a custom-made gold-coated endovascular ICD. Indeed, the tendency is an initial misdiagnosis as an infection and a high clinical suspicion is essential to an early diagnosis.

Cysteine is a better predictor of coronary artery disease than conventional homocysteine in high-risk subjects under preventive medication.

BACKGROUND AND AIMS: In Portugal, The Azores Archipelago has the highest standardized mortality rate for CAD. Therefore, the aim of this study was to evaluate conventional risk factors, as well as plasma and erythrocyte aminothiol concentration in high-risk Azorean patients undergoing elective coronary angiography and to investigate whether any aminothiol was associated with CAD risk and severity. METHODS AND RESULTS: 174 subjects with symptomatic CAD (age 56±9y; 68% men) submitted to coronary angiography were split into 2 groups: one formed by CAD patients (≥50% stenosis in at least one major coronary vessel) and the other by non-CAD patients (<50% stenosis). Both groups were age-, sex- and BMI-matched. Plasma and erythrocyte aminothiol profiles were evaluated by RP-HPLC/FLD. CAD patients significantly exhibited both higher concentrations of plasma Cys and hypercysteinemia (Cys ≥ 300 µM) prevalence than those in the non-CAD group (261 ± 58 µM vs. 243 ± 56 µM; 22% vs. 10%, respectively). No differences were observed between groups regarding plasma Hcy levels or hyperhomocysteinemia prevalence. After adjustment for several confounders (including Hcy), subjects in the highest quartile of plasma Cys had a 3.31 (95% CI, 1.32-8.30, p = 0.011) fold risk for CAD, compared with those in the lowest quartiles. Furthermore, plasma Cys levels (but not Hcy) tended to increase with the number of stenotic vessels (1VD: 253 ± 64 µM; 2VD: 262 ± 52 µM; 3VD: 279 ± 57 µM, p = 0.129). CONCLUSION: Hypercysteinemia revealed to be a better predictor of CAD than hyperhomocysteinemia. Moreover, plasma Cys showed to be a useful biomarker for CAD both in primary and secondary preventions, seeming to resist better than Hcy to oral medication therapy.

Anticancer Potential of Resveratrol, ß-Lapachone and Their Analogues.

This review aims to explore the potential of resveratrol, a polyphenol stilbene, and beta-lapachone, a naphthoquinone, as well as their derivatives, in the development of new drug candidates for cancer. A brief history of these compounds is reviewed along with their potential effects and mechanisms of action and the most recent attempts to improve their bioavailability and potency against different types of cancer.

Distinct modulatory role of RNA in the aggregation of the tumor suppressor protein p53 core domain.

Inactivation of the tumor suppressor protein p53 by mutagenesis, chemical modification, protein-protein interaction, or aggregation has been associated with different human cancers. Although DNA is the typical substrate of p53, numerous studies have reported p53 interactions with RNA. Here, we have examined the effects of RNA of varied sequence, length, and origin on the mechanism of aggregation of the core domain of p53 (p53C) using light scattering, intrinsic fluorescence, transmission electron microscopy, thioflavin-T binding, seeding, and immunoblot assays. Our results are the first to demonstrate that RNA can modulate the aggregation of p53C and full-length p53. We found bimodal behavior of RNA in p53C aggregation. A low RNA:protein ratio (∼1:50) facilitates the accumulation of large amorphous aggregates of p53C. By contrast, at a high RNA:protein ratio (≥1:8), the amorphous aggregation of p53C is clearly suppressed. Instead, amyloid p53C oligomers are formed that can act as seeds nucleating de novo aggregation of p53C. We propose that structured RNAs prevent p53C aggregation through surface interaction and play a significant role in the regulation of the tumor suppressor protein.

Thrombus aspiration in patients with ST-elevation myocardial infarction: results of a national registry of interventional cardiology.

BACKGROUND: We aimed to evaluate the impact of thrombus aspiration (TA) during primary percutaneous coronary intervention (P-PCI) in 'real-world' settings. METHODS: We performed a retrospective study, using data from the National Registry of Interventional Cardiology (RNCI 2006-2012, Portugal) with ST-elevation myocardial infarction (STEMI) patients treated with P-PCI. The primary outcome, in-hospital mortality, was analysed through adjusted odds ratio (aOR) and 95% confidence intervals (95%CI). RESULTS: We assessed data for 9458 STEMI patients that undergone P-PCI (35% treated with TA). The risk of in-hospital mortality with TA (aOR 0.93, 95%CI:0.54-1.60) was not significantly decreased. After matching patients through the propensity score, TA reduced significantly the risk of in-hospital mortality (OR 0.58, 95%CI:0.35-0.98; 3500 patients). CONCLUSIONS: The whole cohort data does not support the routine use of TA in P-PCI, but the results of the propensity-score matched cohort suggests that the use of selective TA may improve the short-term risks of STEMI.

A devices' game of thrones: cardiac resynchronization therapy vs. pacemaker.

AIMS: Oversensing can interfere with biventricular pacing. Cardiac Resynchronization Therapy (CRT) output inhibition due to automatic brady mode change from a sensing to a pacing mode of a previously implanted pacemaker as it reached battery capacity depleted indicator has not been previously published in the medical literature. METHODS AND RESULTS: We report the first case of CRT output inhibition in a pacemaker dependent patient due to electrical stimuli from a previously right-sided implanted pacemaker, after unaware reversion of OVO mode (O = no chambers paced; V = ventricular sensing; O = no response to sensing) to backup VVI (V = ventricular pacing; V = ventricular sensing; I = inhibitory response to sensing) when it reached the elective replacement interval. CONCLUSION: This paper emphasizes the importance of knowing the distinct pacemaker brady mode behaviours after battery capacity depleted indicator has been reached, according to the pacemakers' manufacturer, including the possibility of automatic brady mode change from sensing to pacing mode. It also highlights the potential for severe bradycardia or asystole of this automatic brady mode change from a previously implanted pacemaker in pacemaker dependent patients submitted to CRT upgrade.

Dabigatran reversal with idarucizumab in a patient undergoing heart transplantation: first European report.

BACKGROUND: Dabigatran is a direct thrombin inhibitor with a favorable effectiveness and safety profile when compared to vitamin K antagonists, both in randomized trials and real world registries of atrial fibrillation patients. Yet, physicians' fear of high bleeding risk scenarios in daily clinical practice still precludes a more widespread use of oral anticoagulation. We hereby report a successful case of dabigatran reversal with the novel monoclonal antibody fragment idarucizumab in a patient undergoing heart transplantation. CASE PRESENTATION: A 45-year old male patient on dabigatran for atrial fibrillation thromboprophylaxis was enlisted for heart transplantation due to end-stage ischemic heart failure. Upon donor availability and suitability and following the last intake of the drug 12 h previously, activated partial thromboplastin time was measured and found to be elevated. After general anesthesia and before extracorporeal circulation, idarucizumab was administered as two boluses of 2.5 g. Orthotopic heart transplantation ensued under full heparinization and cardiopulmonary bypass. Total chest tube output was 1125 mL after 3 days and 4 units of fresh frozen plasma and one platelet pool were administered in the operating room without further need for blood products. The post-operative period was uneventful. CONCLUSIONS: Idarucizumab was associated with an effective hemostasis in the setting of heart transplantation. Dabigatran may be considered as an alternative to vitamin K antagonists in heart transplant candidates with an indication for oral anticoagulation.

Heart surgery waiting list management in an ultra-peripheral region: impact of a risk-stratified queuing method.

BACKGROUND: The management of heart surgery waiting list is essential, particularly in ultraperipheral regions. We aimed to characterise a cohort of patients awaiting surgery in such a region, and to assess the occurrence of adverse events and causative factors. METHODS: A retrospective, multicentre analysis from 2016 to 2020. Patients were divided into "Urgent group" vs "Priority group" based on surgical priority. A composite outcome of death or hospital admission was determined. RESULTS: We included 329 patients, 18.2% in the Urgent group. Baseline characteristics were similar, except for a higher prevalence of smoking habits in the Urgent group (56.7% vs 38.7%, p = 0.016), as well as the CCS class (p = 0.014) and EuroScore surgical risk (p < 0.001). Disease acuity indicated highest priority for coronary artery bypass grafting patients. Myocardial revascularization and aortic valvular replacement were the main procedures. Overall, 15.2% of patients received treatment within recommended waiting time, with 50.8% being Urgent patients. Urgent patients had higher risk for composite outcome (HR 3.92, 95% CI 1.26-12.22; p = 0.019), with fewer events reported (5% vs 17.8%, p = 0.051). Chronic kidney disease and previous open-heart surgery were independent predictors of this outcome. Chronic kidney disease remained as independent predictor at 1-year follow-up, while surgical priority did not affect outcomes. CONCLUSIONS: Despite similar occurrences of adverse events on the waiting list, longer waiting times for patients in the Urgent group increase their risk of adverse events. The priority level had no impact on outcomes. Chronic kidney disease and open-heart surgery were independent predictors for events, highlighting their significance in the triage process.

Systemic disease presenting as cardiac tamponade: a case report.

Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by multisystem inflammation and is a common cause of pericarditis and pericardial effusion, but significant pericardial effusion and cardiac tamponade are rare and even rarer as the first manifestation. Case summary: We report the case of a young male who presented with fever, recurrent pericarditis, and polyserositis with pericardial and bilateral pleural effusion. On examination, he was haemodynamically unstable and the pericardial effusion had considerable dimensions and an urgent pericardiocentesis was performed. Antinuclear antibody with a speckled pattern was positive, complement C4 levels were low, and the remaining autoimmunity and infectious study was unremarkable. Considering the European League Against Rheumatism/American College of Rheumatology classification criteria for SLE, a score of 11 points was obtained, confirming the diagnosis of SLE. Discussion: This case report illustrates a rare form of presentation of SLE, in which the first manifestation was pericarditis with polyserositis and cardiac tamponade.

Primary cardiac lymphoma: The unusual suspect and the importance of a multimodality approach.

Primary cardiac lymphomas are rare tumors with heterogeneous presentation, often difficult to diagnose, requiring a high level of clinical suspicion. An attempted diagnosis is fundamental for effective treatment. We report a very rare case of a primary cardiac lymphoma in a middle-age female patient that presented with atrial flutter, atrioventricular conduction disorder, and a secondary autoimmune hemolytic anemia with cold agglutinin syndrome. The investigation was challenging and a definite diagnosis was achieved by histopathological study and corroborated by regression after chemotherapy. Learning objectives: Primary cardiac tumors are rare, often difficult to diagnose, and a multimodality imaging approach is essential for diagnosis. Although complete atrioventricular (AV) block is often an indication for permanent pacemaker, reversible causes should be considered. AV blocks caused by infiltration of lymphoma can resolve after effective treatment and so it may be reasonable to delay pacemaker implantation until after treatment. A multidisciplinary approach is fundamental in complex cases.

Impact of the COVID-19 pandemic on percutaneous coronary interventions in Portugal.

INTRODUCTION: The COVID-19 pandemic has imposed an unprecedented burden on healthcare systems worldwide, changing the profile of interventional cardiology activity. OBJECTIVES: To quantify and compare the number of percutaneous coronary interventions (PCIs) performed for acute and chronic coronary syndromes during the first COVID-19 outbreak with the corresponding period in previous years. METHODS: Data on PCI from the prospective multicenter Portuguese Registry on Interventional Cardiology (RNCI) were used to analyze changes in PCI for ST-elevation myocardial infarction (STEMI), non-ST-elevation acute coronary syndromes (NSTE-ACS) and chronic coronary syndromes (CCS). The number of PCIs performed during the initial period of the COVID-19 outbreak in Portugal, from March 1 to May 2, 2020, was compared with the mean frequency of PCIs performed during the corresponding period in the previous three years (2017-2019). RESULTS: The total number of PCIs procedures was significantly decreased during the initial COVID-19 outbreak in Portugal (-36%, p<0.001). The reduction in PCI procedures for STEMI, NSTE-ACS and CCS was, respectively, -25% (p<0.019), -20% (p<0.068) and -59% (p<0.001). CONCLUSIONS: Compared with the corresponding period in the previous three years, the number of PCI procedures performed for STEMI and CCS decreased markedly during the first wave of the COVID-19 pandemic in Portugal.

PRIMA-1 inhibits Y220C p53 amyloid aggregation and synergizes with cisplatin in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. Although many therapeutic options are available, several factors, including the presence of p53 mutations, impact tumor development and therapeutic resistance. TP53 is the second most frequently mutated gene in HCC, comprising more than 30% of cases. Mutations in p53 result in the formation of amyloid aggregates that promote tumor progression. The use of PRIMA-1, a small molecule capable of restoring p53, is a therapeutic strategy to pharmacologically target the amyloid state mutant p53. In this study, we characterize an HCC mutant p53 model for the study of p53 amyloid aggregation in HCC cell lines, from in silico analysis of p53 mutants to a 3D-cell culture model and demonstrate the unprecedented inhibition of Y220C mutant p53 aggregation by PRIMA-1. In addition, our data show beneficial effects of PRIMA-1 in several "gain of function" properties of mutant-p53 cancer cells, including migration, adhesion, proliferation, and drug resistance. We also demonstrate that the combination of PRIMA-1 and cisplatin is a promising approach for HCC therapy. Taken together, our data support the premise that targeting the amyloid-state of mutant p53 may be an attractive therapeutic approach for HCC, and highlight PRIMA-1 as a new candidate for combination therapy with cisplatin.

[Streptococcus agalactiae endocarditis]. / Endocardite a Streptococcus agalactiae.

Streptococcus agalactiae endocarditis is a rare clinical entity that is generally characterized by acute onset, the presence of large vegetations, rapid valvular destruction and frequent complications, particularly embolization. Mortality is high with medical therapy alone. The authors present a case report of Streptococcus agalactiae endocarditis in a young patient treated by prompt surgery. The literature is reviewed.

[Coronary artery anomalies]. / Anomalias das artérias coronárias.

Coronary artery anomalies (CAAs) are a rare entity but their true incidence in the general population has yet to be determined. Most CAAs are asymptomatic, but they are nevertheless the second leading cause of sudden death in apparently healthy young athletes. The new imaging methods available to cardiologists, including CT angiography and MRI, now enable noninvasive diagnosis and characterization of these anomalies. The authors review the literature and present a retrospective study of 360 consecutive patients who underwent cardiac CT angiography. Demographic, clinical and angiographic characteristics were studied. The incidence of CAAs in this population was 2.69%. In order to better characterize this disorder, including diagnostic strategy, screening, treatment and prognosis, the authors suggest the establishment of a national registry of cardiac CT angiography. Such a registry would fill the existing gap in information on exams performed in the country, enriching current knowledge about this disease and noninvasive cardiac imaging in Portugal.

Double coronary anomaly: A case report.

We describe an extremely rare case of a 37-year-old female patient who presented with exertional angina and was diagnosed with a unique coronary anomaly with an anomalous right coronary artery with origin in the left anterior descending artery and a fistula between this anomalous coronary artery and the pulmonary artery. Learning objectives: Most patients with coronary anomalies are asymptomatic but some may have angina caused by a coronary steal phenomenon, myocardial infarction, or even sudden death depending on the circuit and characteristics of the anomaly.The combination of multiple coronary anomalies is extremely rare.Despite being a rare diagnosis, coronary anomalies should always be considered as a cause of myocardial ischemia, especially in young patients with low probability for coronary obstructive disease.

Worrisome trends of ST-elevation myocardial infarction during the Covid-19 pandemic: Data from Portuguese centers.

Introduction: During the Covid-19 pandemic there has been a general belief that hospital admissions for non-infectious causes, especially cardiovascular diseases, have fallen. Objectives: To assess the impact of the pandemic on admissions for ST-elevation myocardial infarction (STEMI) during the first pandemic wave. Methods: We performed a multicenter retrospective analysis of consecutive patients presenting with STEMI in two Portuguese hospital centers in two sequential periods - P1 (March 1 to April 30) and P2 (May 1 to June 30). Patient's clinical data and hospital outcomes were compared between the years 2017 to 2019 and 2020 for both periods. Results: During P1 in 2020, a reduction in the number of STEMI patients was observed in comparison with previous years (26.0±4.2 vs. 16.5±4.9 cases per month; p=0.033), as well as an increase in the number of mechanical complications (0.0% vs. 3.0%; p=0.029). Percutaneous coronary interventions in the setting of failed thrombolysis were more frequent (1.9% vs. 9.1%; p=0.033). An overall trend for longer delays in key timings of STEMI care bundles was noted. Mortality was higher during P1 compared to previous years (1.9% vs. 12.1%; p=0.005). Conclusions: During the first Covid-19 wave fewer patients presented with STEMI at the catheterization laboratory for percutaneous coronary intervention. These patients presented more mechanical complications and higher mortality.

Introdução: Recentemente durante a pandemia por Covid-19 houve uma perceção global de uma diminuição de admissões hospitalares por causas não infeciosas, em particular por doenças cardiovasculares. Objetivos: Avaliar o impacto da pandemia nas admissões por enfarte agudo do miocárdio com supradesnivelamento de ST (STEMI), na primeira onda da pandemia. Métodos: Análise multicêntrica e retrospetiva de doentes consecutivos admitidos em dois hospitais portugueses por STEMI em dois períodos sequenciais - P1 (1 de março a 30 de abril) e P2 (1 de maio a 30 de junho). Foi realizada uma comparação dos dados clínicos e de evolução hospitalar entre 2017 a 2019 e 2020 para os dois períodos. Resultados: No P1 de 2020 observou-se, relativamente a anos prévios, uma redução do número de doentes com STEMI (26,0±4,2 versus 16,5±4,9 casos por mês; p=0,033) e um aumento do número de complicações mecânicas (0,0% versus 3,0%; p=0,029). Os casos de angioplastia após trombólise falhada foram mais frequentes (1,9% versus 9,1%; p=0,033). Observou-se uma tendência global para um maior atraso nos tempos-chave de abordagem de doentes com STEMI. A taxa de mortalidade destes doentes no P1 foi superior comparativamente a anos prévios (1,9% versus 12,1%; p=0,005). Conclusões: Durante a primeira onda da pandemia Covid-19 houve uma redução do número de doentes submetidos a angioplastia coronária por STEMI. Esses apresentaram mais complicações mecânicas e uma maior mortalidade.

Circulating antioxidant vitamins and copper in Azorean coronary artery disease patients under preventive medication - A case study.

BACKGROUND AND AIM: Oxidative stress and inflammation are conditions that are deeply involved in atherosclerosis and consequent coronary artery disease (CAD). Therefore, the aim of this study was to assess the relationship among circulating antioxidant vitamins (C, A, E), copper, and other pro- or antioxidant/inflammation markers in patients with and without CAD under preventive medication. SUBJECTS AND METHODS: 174 Azorean subjects symptomatic for CAD (age 56 ± 9y; 68 % men) submitted to coronary angiography were split into 2 groups: one formed by CAD patients (≥50 % stenosis in at least one major coronary vessel) and the other by non-CAD patients (<50 % stenosis). Both groups were age-, sex- and BMI-matched. Plasma levels of vitamins or copper were measured by HPLC and AAS, respectively. RESULTS AND CONCLUSIONS: Lower vitamin C levels were observed in CAD patients (mainly in women, who exhibited a high rate of diabetes mellitus) as compared to the non-CAD ones. Also, CAD patients (mainly men) exhibited significantly higher concentrations of plasma copper than their non-CAD counterparts (1.17 ± 0.3 mg/L vs. 1.09 ± 0.3 mg/L, p = 0.030). In bivariate analysis, plasma copper levels were positively associated with serum LDL-cholesterol (r=0.22; p = 0.004) and chiefly with C-reactive protein (r=0.40; p < 0.001). Furthermore, they were significantly lower in recurrent vs. non recurrent CAD patients (1.07±0.2 vs. 1.24±0.3 mg/L, p = 0.004). ROC analysis showed that plasma copper, whenever >1.06 mg/L, was an independent risk factor for CAD in primary prevention for men, which suggests that its levels can fluctuate with medical therapy (such as anti-inflammatory), thus indicating that copper is not a reliable marker for CAD. Moreover, plasma copper concentration was not associated with CAD severity. Yet, results do suggest that, even within its reference concentration range, it could be useful as an acute inflammation marker in CAD management.

Epidermal growth factor receptor regulates fibrinolytic pathway elements in cervical cancer: functional and prognostic implications.

Epidermal growth factor receptor (EGFR) signaling and components of the fibrinolytic system, including urokinase-type plasminogen activator (uPA) and thrombomodulin (TM), have been implicated in tumor progression. In the present study, we employed cBioPortal platform (http://www.cbioportal.org/), cancer cell lines, and an in vivo model of immunocompromised mice to evaluate a possible cooperation between EGFR signaling, uPA, and TM expression/function in the context of cervical cancer. cBioPortal analysis revealed that EGFR, uPA, and TM are positively correlated in tumor samples of cervical cancer patients, showing a negative prognostic impact. Aggressive human cervical cancer cells (CASKI) presented higher gene expression levels of EGFR, uPA, and TM compared to its less aggressive counterpart (C-33A cells). EGFR induces uPA expression in CASKI cells through both PI3K-Akt and MEK1/2-ERK1/2 downstream effectors, whereas TM expression induced by EGFR was dependent on PI3K/Akt signaling alone. uPA induced cell-morphology modifications and cell migration in an EGFR-dependent and -independent manner, respectively. Finally, treatment with cetuximab reduced in vivo CASKI xenografted-tumor growth in nude mice, and decreased intratumoral uPA expression, while TM expression was unaltered. In conclusion, we showed that EGFR signaling regulated expression of the fibrinolytic system component uPA in both in vitro and in vivo settings, while uPA also participated in cell-morphology modifications and migration in a human cervical cancer model.