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Abstract The objective of this study was to investigate the relationship of insulin‐like growth factor 2 (IGF2) expression and survival in women with uterine carcinosarcoma (UCS). Insulin‐like growth factor 2 protein expression was determined by immunohistochemical staining of tumor tissues from 103 patients with UCS. The H‐score (product of staining intensity and percentage positive cells) was quantified for the epithelial cytoplasmic (EC), epithelial nuclear (EN), and malignant stromal compartments. Multivariable Cox proportional hazard regression models were used to examine the relationship of IGF2 levels with progression‐free survival (PFS) and overall survival (OS). Adjusting for stage, race, and adjuvant therapy, PFS and OS were reduced in patients with high IGF2 (H‐score ≥ median) in the EC and EN compartments. Black race was independently associated with reduced PFS and OS in patients with early‐stage disease, and IGF2 levels in the EC were higher in black than in white patients (P = 0.02, Wilcoxon test). In a race‐stratified multivariable analysis, high IGF2 in the epithelial compartments more than doubled the risk of death in black women; HR = 2.43 (95% CI: 1.18–5.01, P = 0.02) for high IGF2 in the EC; and HR = 2.34 (95% CI: 1.25–4.39, P = 0.008) for high IGF2 in the EN. In conclusion, high tumor IGF2 expression is an independent risk factor for reduced PFS and OS in UCS. Black women have elevated tumor IGF2 compared with white women, and decreased survival associated with high IGF2. These findings identify IGF2 as a candidate biomarker for survival linked to racial disparity in women with UCS.

Drug resistance is an obstacle to the effective treatment of ovarian cancer. We and others have shown that the insulin-like growth factor (IGF) signaling pathway is a novel potential target to overcome drug resistance. The purpose of this study was to validate IGF2 as a potential therapeutic target in drug resistant ovarian cancer and to determine the efficacy of targeting IGF2 in vivo. An analysis of The Cancer Genome Atlas (TCGA) data in the serous ovarian cancer cohort showed that high IGF2 mRNA expression is significantly associated with shortened interval to disease progression and death, clinical indicators of drug resistance. In a genetically diverse panel of ovarian cancer cell lines, the IGF2 mRNA levels measured in cell lines resistant to various microtubule-stabilizing agents including Taxol were found to be significantly elevated compared to the drug sensitive cell lines. The effect of IGF2 knockdown on Taxol resistance was investigated in vitro and in vivo. Transient IGF2 knockdown significantly sensitized drug resistant cells to Taxol treatment. A Taxol-resistant ovarian cancer xenograft model, developed from HEY-T30 cells, exhibited extreme drug resistance, wherein the maximal tolerated dose of Taxol did not delay tumor growth in mice. Blocking the IGF1R (a transmembrane receptor that transmits signals from IGF1 and IGF2) using a monoclonal antibody did not alter the response to Taxol. However, stable IGF2 knockdown using short-hairpin RNA in HEY-T30 effectively restored Taxol sensitivity. These findings validate IGF2 as a potential therapeutic target in drug resistant ovarian cancer and show that directly targeting IGF2 may be a preferable strategy compared with targeting IGF1R alone.

Background: Increased systolic pulmonary arterial pressure (sPAP) could lead to the mechanical dysfunction and myocardial fibrosis of the right heart chambers. Echocardiographic strain analysis has not been adequately studied in patients with pulmonary hypertension (PH)., Study Design and Methods: A cross-sectional cohort of patients with suspected PH and echocardiographic strain evaluation was recruited. The cut-off values of peak tricuspid regurgitation velocity (TRV) with the low probability of PH (≤2.8 m/s), intermediate probability (2.9-3.4 m/s, without other echo PH signs), and high probability of PH (2.9-3.4 m/s with other echo PH signs and >3.4 m/s) categories were studied by right ventricular and right atrial (RA) strain analysis in a sample of 236 patients., Results: The results showed that 58 (56.9%) patients had low, 15 (14.7%) had intermediate, and 29 (28.4%) had a high probability of PH. We observed a negative association between right ventricular free wall strain (RV-FWS) and atrial global strain with sPAP. With the increase in PH severity, RA reservoir, conduit, and contraction (booster) strain values decreased. The identified cut-off values of strain parameters had an adequate ability to detect PH severity categories. In addition, the post-mortem biopsies of right heart chambers from subjects with known severe PH were analyzed to quantify myocardial fibrosis. Our sample of right heart biopsies ( n = 12) demonstrated an association between increased sPAP before death and right ventricular and RA fibrosis., Conclusion: Mechanical dysfunction and fibrosis in the right chambers are associated with increased sPAP. Right ventricular and atrial strain could provide enhancement in the diagnosis and categorization of subjects with suspected PH., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Espinola-Zavaleta, Antonio-Villa, Guerra, Nanda, Rudski, Alvarez-Santana, Camacho-Camacho, Aranda-Fraustro, Cossio-Aranda, Zamora, Oregel-Camacho, Armenta-Moreno, Berarducci and Alexanderson-Rosas.)

Background: Cerebral venous thrombosis (CVT) is a rare medical condition that primarily affects young adults. The clinical spectrum is broad and its recognition remains a challenge for clinicians. Limited information is available on CVT in Argentina. Our goal was to report the results of the first National registry on CVT in Argentina and to compare clinical presentation, predisposing factors and outcomes with other international registries., Material and Method: The Argentinian National Registry on CVT (ANR-CVT) is a multicenter retrospective cohort study comprising patients aged 18 and older with a diagnosis of CVT from January 2015 to January 2019. We evaluated demographics, predisposing factors, clinical presentation, and radiological characteristics (e.g. number of involved sinuses, venous infarction or hemorrhage on CT and MRI scans at admission), therapeutic interventions and functional outcomes at discharge and at 90 days. Our results were compared to a literature review of CVT registries., Results: Overall, one hundred and sixty-two patients met the inclusion criteria. The mean age was 42 (±17) years; 72% were women. Seventy percent of patients were younger than 50 years. The most common presenting symptom was headache (82%). The transverse sinus was the most common site of thrombosis (70%) followed by the sigmoid sinus (46%). The main predisposing factor in women was contraceptive use (44%), 3% of the events occurred during pregnancy and 9% during the puerperium. Participants 50 years and older had a higher frequency on malignancy related (7.5% vs. 30%, p = 0.0001) and infections (2% vs. 11%, p = 0.001). The modified Rankin Scale (mRS) ≤2 at discharge was 81% and the rate of mortality at discharge was 4%. At 90 days, the mRS≤2 was 93%. When the ANR-CVT was compared with larger registries from Europe and Asia, the prevalence of cancer among patients with CVT was two to five-fold higher (15% vs. 7% and 3%, respectively; p = 0.002 and p < 0.001). Anticoagulation rates at discharge were also higher (94%) compared to registries from Asia (ASCVT - 68%) or Turkey (VENOST - 67%)., Conclusion: Participants in the first ANR-CVT had a low mortality and disability at 90 days. Clinical and radiological characteristics were similar to CVT from other international registries with a higher prevalence of cancer. There was a high variability in treatment adherence to guidelines as reflected by anticoagulation rates (range 54.5%-100%) at discharge., Competing Interests: Declaration of Competing Interest All authors certify that they have no affiliations with or involvement in any organization or entity with any financial or nonfinancial interest in the subject matter or materials discussed in this manuscript., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Overweight and obesity (O/O) generate lipotoxicity of the cardiac fiber and increase the incidence and progression of aortic valve stenosis. The low cardiac output syndrome (LCOS) is a timing complication after to aortic valve replacement (AVR) surgery., Objective: The objective of the study was to investigate if body mass index (BMI) kg/m 2 is a risk factor associated with LCOS and mortality in the post-operative period of AVR., Methods: A historic cohort study was designed, including patients with severe aortic stenosis (SAS), who were subjected to AVR., Results: 152 patients were included, 45 (29.6%), with normal weight (NW), 60 were overweight (39.5%), and 47 obese (30.9%). The prevalence of systemic hypertension (HT) was higher in O/O (p < 0.0001). Incidence of LCOS was 44.7%, being more frequent in the O/O groups compared to the NW group, 43.3%, 68.1%, and 22.2%, respectively, (p < 0.05 in overweight and p < 0.0001 in the obese). Assessing the presence or absence of LCOS associated with BMI as a numerical variable, we found that women, HT, BMI, left ventricular mass, and valve size, were associated with LCOS (p < 0.02, p < 0.02, p < 0.001, p < 0.032, and p < 0.045, respectively). Mortality was higher in patients who had LCOS (p < 0.02). Multivariate model showed that BMI was an independent risk factor for LCOS (odds ratio [OR] 1.21 [95% CI 1.08-1.35], p < 0.001)., Conclusion: BMI is a risk factor associated to LCOS in the post-operative period of AVR in patients with SAS., (Copyright: © 2020 Permanyer.)

The COVID-19 pandemic has had major negative health, psychological, social and economic repercussions for individuals, families, communities, countries and for humanity in general. The interrelation with age and the presence of chronic non-communicable diseases (hypertension, diabetes, obesity, smoking) seems to go further than what would be explained by the prevalence and distribution of both. The drugs that act on the renin-angiotensin-aldosterone system are in many cases the backbone for the management of these diseases, it has been known for a long time that these drugs significantly increase the expression of receptors for angiotensin conversion enzyme type 2 in the lung tissue. This fact, together with the knowledge that the route of entry of the virus into the cell is precisely the ACE-2 receptor, initiated a hypothesis, based on very low-quality evidence, which quickly became generalized in the media, that the use of these drugs could be negative and that they should be interrupted immediately. The response of practically all Scientific Societies was almost immediate, with the precise indication that treatment with these drugs should not be discontinued, since the evidence of their usefulness is based on very solid and high-quality evidence. Simultaneously, a different hypothesis also appeared, also based on very preliminary evidence, that these drugs are not only harmful but also beneficial, however these medicaments are not yet accepted as agents for the prevention or treatment of this disease or its complications. This review reports current knowledge on the relationship between COVID-19 and SRAA., (Copyright: © 2020 Permanyer.)

Heart failure (HF) is a syndrome characterized basically by a circulatory deficit to cover the metabolic and energetic demands of the body. This condition has a broad spectrum in its clinical presentation, affects the quality of life significantly, impacts the family/social environment, and generates a great demand for health services. The purpose of this research is to report the situational diagnose of patients with HF in Mexico. We evaluated 292 patients, 70.2% were men. Average age was 56.7 ± 14.3 years. Ischemic heart disease is the main etiology (98 patients, 33.9%) followed by hypertensive (22.6%) and idiopathic (23.3%) heart disease. The associated clinical background was obesity (31.1%), systemic hypertension (36.7%), myocardial infarction (26.4%), and dyslipidemia (15.1%). The most common symptom was stress dyspnea (41.4%) and jugular vein engorgement at physical examination (32.5%). Anemia was observed in 1% of patients. The average left ventricular ejection fraction was 29.2 ± 10.6%. Sinus rhythm was the most frequently detected in 84.9%. 19.9% of patients had an implantable cardioverter-defibrillator or cardiac resynchronization therapy. 13.7% of patients with QRS > 130 ms. In our population, the meta-analysis global group in chronic heart failure risk score calculated was 16.8 ± 5.7 and for EMPHASIS 3.3 ± 1.5. We observed that age at presentation in HF in this analysis is at least 10 years younger than in other reports. The grade of obesity takes relevance in our group. The association of anemia and HF in Mexico is rare., (Copyright: © 2019 Permanyer.)

Background: In Ebstein's anomaly (EA) current surgical criteria may not translate into better long-term survival. The aim of this study was therefore to determine if surgical treatment for EA increases survival, and to analyze factors associated with mortality., Methods and results: A retrospective study was carried out involving 103 patients with surgical indication using current criteria, comparing operated (n=49; 47.5%) and non-operated patients (n=54; 52.4%); the severity of disease was similar in all cases. Overall follow-up was 12 years (range, 1-49 years). There were no differences in mortality: in the surgical and non-surgical groups, survival at 10 years was 92.8% vs. 90.7%; 20 years, 85.7% vs. 81.0%; and 30 years, 78.5% vs. 72.2%, respectively. On multivariate analysis right ventricular fractional shortening (RVFS) was associated with mortality in both groups. Decreasing RVFS was associated with worse survival according to severity: when RVFS was <20%, survival at 20, 40 and 60 years was 58%, 39%, and 12.5%, respectively (P<0.0013). Left ventricular ejection fraction also correlated with survival (P<0.0013)., Conclusions: Surgery did not translate into benefit in terms of survival, and this was clearly associated with RV function; therefore this should be a key factor in the surgical decision making.

When aneurysm of the root of aorta, bicuspid aorta valve and coarctation coexist, surgical repair involves technical problems. We present the case of a patient in whom initial correction of the coarctation was made by means of interventional treatment, with an impressive and practically immediate resolution of heart failure. In a second intervartional, the aortic root pathology was corrected through the Bentall and de Bono's surgical technique. We present the short- and mid-term results. In addition this case demostrates the little well-know fact, that the patients with bicuspid aorta also have cystic media degeneration of the wall of the aorta.

Background: The relationship between myocardial bridging (MB) and ischemic heart disease is still controversial. However, a recent new evidence suggests that this relation is not by chance., Purpose: The purpose of our study was to review in a critical manner, the evidence for the relationship between MB and myocardial ischemia and its possible consequences., Methods: We present 2 cases of our series and review the medical literature from January 1966 to January 1998 published and included in Medline and Current Contents., Results and Conclusions: The principal findings after this review were: 1) MB is not a normal variant; 2) The clinical impact of MB depends on its anatomical extension and degree of compressive effect; 3) The MB muscle is not similar to myocytes from other cardiac areas; 4) The environment surrounding coronary artery may be a crucial factor in determining whether the MB influences the induction of heart disorders or not; 5) The overshoot due to compressive effect on coronary artery might determine endothelial injury in the microcirculation post-MB; 6) In some cases, the systolic endothelial injury may contribute to release factors that are able to reduce the coronary reserve, resulting in myocardial ischemia; 7) The possible role of PTCA in this disorder still has to be proven. Surgical treatment should be considered when important myocardial ischemia had been demonstrated, even in those asymptomatic cases.

Objectives: The purpose of this study was to determine whether infarct-related coronary artery patency influences myocardial electrical stability as measured by the prevalence of late potentials or heart rate variability., Background: Several studies have suggested that loss of vagal activity is associated with an increased incidence of arrhythmic death after myocardial infarction., Methods: A short-duration, high resolution electrocardiogram (ECG) was performed before hospital discharge in 175 patients with a first myocardial infarction. Seventy-three patients received thrombolytic therapy. All patients underwent coronary angiography. Coronary occlusion was defined as minimal or no anterograde flow. Eighty-eight patients (50.3%) had an occluded infarct-related artery. Sixty-two healthy subjects served as control subjects to determine the normal range of heart rate variability., Results: Comparison between the control group and patients without patency of the infarct-related artery in the time domain and spectral analyses revealed in the latter patients a reduced heart rate variability (p < 0.0001) and a lower power spectrum density in both the 0.05- to 0.15-Hz band (p < 0.0001) and the 0.15- to 0.35-Hz band (p < 0.0001). The heart rate variability in patients with late potentials was lower than in those with a normal signal-averaged ECG. Those patients with spontaneous or thrombolysis-induced reperfusion have less occurrence of late potentials and higher parasympathetic activity than do patients with a closed artery., Conclusions: This study suggests that the patency of the infarct-related artery determines both the absence of late potentials and the preservation of vagal tone and may explain the reduction in mortality induced by thrombolytic therapy in myocardial infarction.