Interleukin-12 treatment reduces tumor growth and modulates the expression of CASKA and MIR-203 in athymic mice bearing tumors induced by the HGC-27 gastric cancer cell line.

Gastric cancer (GC) is one of the most common malignant tumors in the digestive system and due to its poor prognosis, there is an increase in the demand for more effective anticancer therapies. Interleukins are potential anticancer agents which can modulate expression of cancer related genes and have therapeutic effects. Interleukin 12 (IL-12) exhibits potent anti-tumor, anti-angiogenic and anti-metastatic activities and represents the ideal candidate for tumor immunotherapy, due to its ability to activate both innate and adaptive immunities. The aim of this study was to evaluate the effect of IL-12 administration on GC tumor growth induced in the cancer xenograft nude mouse model. Tumor development was analyzed weekly and after 8 weeks, the animals were sacrificed for cytokine analysis (IL-4, TNF-alfa, IL-2, INF-gamma, IL-12, IL-10, TGF-beta) by ELISA. The tumor cells in the implanted areas of the animals that developed solid growth of the tumor (anatomopathological analysis was performed). We have also evaluated CASK and miR203 expression, two related cell invasion factors, in the induced tumors after administration of 6 n/kg IL-12. The development of tumor masses was observed in all groups of animals inoculated with HGC-27 neoplastic cells. In animals treated with 6 n/kg IL-12, there was no tumor development confirmed by anatomopathological analysis. Changes in the levels of pro and anti-inflammatory cytokines were also observed. Our results indicated that miR203 expression was elevated while CASK was downregulated. These results suggest that IL-12 treatment repress the tumor growth by induction of miR203 expression which in turn repress CASK expression.

From Shamans to Priests of Sekhmet: A Review of the Literature in Search for the Origins of Doctors in Ancient Egypt.

This review suggests that shamans were in charge of the healing process in pre-dynastic Egypt. After the unification of Lower and Upper Egypt by Narmer in 3100 BC, shamans evolved into the Sem priests, who were responsible for the king's health. With the change in Egyptian religion in the fourth dynasty (2613-2494 BC), Ra, the sun god, was revered as the supreme power, replacing the king. The emergence of mass festivities to celebrate Ra led to the priests of Sekhmet in the fifth dynasty (2494-2345 BC) checking the sanitation of bull meat that was provided to the populace in an attempt to avoid infectious epidemics. This seems to be the first recognition that disease might be transmitted from animals to humans. They used medical folklore, incantations, spells, and charms available at the House of Life, previously used by the lector priest. By 2487 BC, the first medical curative procedure was performed by Ni-Ankh-Sekhmet who cured the bleeding of a king's nose.

A case report of newborn with Klippel-Trenaunay syndrome from mother currently infected by COVID-19.

Background: Coronavirus disease 2019 (COVID-19) novel severe acute respiratory syndrome affected the world population with an infectious condition for which therapeutic forms are limited and vascular sequelae are major challenges. Pregnant women are physiologically immunocompromised and can be more affected by the pandemic than the general population. Extra precaution measures against COVID-19 during and after the outbreak are essential to ensure the safety of the newborn. The aim of the present study was to report the cesarean birth of a female child with Klippel-Trenaunay of a mother currently infected by COVID-19. Case Description: A newborn of a 21-year-old mother with COVID-19 in the final stage of the disease was born through a cesarean section at full term. The physical examination at birth revealed substantial edema of the left lower limb associated with port-wine stains on the limb and left torso. The ultrasound revealed venous-lymphatic malformation affecting the entire left lower limb, suprapubic region and ipsilateral abdominal region. Two evaluations for COVID-19 were performed and both were negative. Infants of mothers with active COVID-19 infection during the birth period have a low probability of being positive for the disease, but precautions should be taken. Conclusions: The association with malformations, such as the rare Klippel-Trenaunay syndrome (KTS), constitutes another challenge regarding the diagnosis and proper conduct to be taken with these children.

Right-Sided Cardiac Thrombosis and Pulmonary Thromboembolism in Chronic Chagas Disease: A Review of Clinical Features and Post-Mortem Examination.

Pulmonary thromboembolism (PE) is a potential major complication in patients with chronic Chagas heart disease (CChD). The source of PE is the right-sided chambers instead of deep vein thrombosis. Little is known regarding risk factors, clinical picture, and the clinical course of patients with PE secondary to CChD. The aim of this review was to try to provide doctors with such data. We searched for papers related to PE in CChD patients in the PUBMED from 1955 to 2020. Twenty-six manuscripts were retrieved, of which 12 fulfilled entry criteria and were included in the study. Right-sided cardiac thrombosis or PE was confirmed on morphological or imaging studies. A total of 431 patients with PE were reported. Age varied from 30 to 85 years. About 332 patients were reported to have chronic heart failure (CHF), whereas 41 (9%) sudden cardiac death (SCD) at autopsy. Clinical manifestations reported were sudden onset dyspnea was found in 1 patient, haemoptysis in 2, worsening CHF in 2, and chest pain in 1. An X-ray chest was reported for 6 patients: abnormalities consistent with PE were found in 3. The resting electrocardiogram (ECG) was reported for 5 patients: it was abnormal in all. One study reported a mean left ventricular ejection fraction of 42.1 ± 18.7%. The prevalence of right-sided cardiac thrombosis varied from 66% to 85% patients. PE was the cause of death in 17% of patients. The clinical diagnosis of PE in patients with Chagas cardiomyopathy (ChCM) is very difficult in the absence of a prediction score that performs well. However, in the presence of haemoptysis or worsening heart failure (HF), abnormal ECG, or chest X-ray, the diagnosis of PE should be raised, and patients promptly referred to detailed Doppler Tissue Echocardiography and computed tomography angiography, and treated in a timely manner.

A Comparison of the Academic Achievement at the End of the Medicine Undergraduate Degree Program Between Students Who Only Used the University Admission Test and Those Who Used the University Admission Test Plus Marks from the High School National Exam (ENEM) at a Single Brazilian Center.

Purpose: The role of marks in the University Admission Test (UAT) plus the marks from pre-university academic records in predicting academic achievement at the end of the Medicine undergraduate degree program is not completely known. This study was undertaken to compare the performance of marks in the UAT alone with those of the UAT plus marks from the National High School Exam (ENEM in Brazil) regarding students' outcomes at the end of the Medicine undergraduate degree program. Methods: Fifty-one (51) students from the last semester (12th) of our Medicine undergraduate degree program were included in the study. They were divided into a group of those who used the marks obtained in the UAT plus the marks obtained in the ENEM (ENEM group, n=9), and those who only used the marks in the UAT (non-ENEM group, n=42). We compared the academic achievement of the non-ENEM group with that of the ENEM group regarding the mean marks obtained in the clerkship, in the Progress Test (PT), and in the Objective Structured Clinical Examination (OSCE). Results: The mean scores obtained in the disciplines of the clerkship were higher in the non-ENEM group compared to the ENEM group (7.32 ± 0.41 vs 6.98 ± 0.31, p= 0.01). Both groups obtained similar mean marks in the OSCE and in the PT. A moderate correlation was observed between the marks in the clerkship with those of the UAT from the non-ENEM group (p=0.00006; r=0.45). Conclusion: Marks of the UAT alone appear to be associated with a higher academic achievement in the clerkship than marks of the UAT plus scores obtained from the ENEM at the end of the Medicine undergraduate degree program.

Plasma Levels of Matrix Metalloproteinases 2 and 9 in Patients with Chronic Chagas Heart Disease and Systemic Arterial Hypertension: Correlation with TGF-Beta Plasma Levels.

Background: Chronic Chagas heart disease (CCHD) and systemic arterial hypertension (SAH) frequently coexists in areas where Chagas disease is endemic. The effects of the association of both conditions (CCHD-SAH) on the extracellular matrix (ECM) remodeling are unknown. Matrix metalloproteinases (MMP) 2 and 9 are involved in ECM remodeling. The aim of this study was to evaluate MMP 2 and MMP9 in CCHD-SAH patients and to correlate their levels with those of the profibrogenic cytokine TGF-beta. Methods: We included 19 patients with CCHD-SAH, 14 patients with CCHD alone, and 19 controls matched by sex and age. MMP-2 and MMP-9 plasma levels were studied by gel zymography and showed as optical densities (OD). TGF-beta plasma levels were measured by double-ligand ELISA and expressed as pg/mL. Results: Median (5th, 95th) MMP-2 plasma levels were 1224.7 OD (1160, 1433.5) in patients with CCHD alone, 1424.1 OD (1267.5, 1561) in patients with CCHD-SAH, and 940 OD (898.1, 1000.8) in controls (p=0.001). MMP-9 plasma levels were 1870 OD (1740, 1904.1) in patients with CCHD alone, 1754.6 OD (1650, 2049) in those with CCHD-SAH and 89.7 OD (80, 96) in controls (p=0.0003). MMP-9 plasma levels were higher than those of MMP 2 in patients with CCHD-SAH (p=0.01). No correlation was found between TGF-beta plasma levels with MMP-2 serum levels (r = 0.12; p=0.7), but a moderate negative correlation (r = -0.46; p=0.048) was observed between TGF-beta and MMP-9 plasma levels. Conclusions: MMP-2 and especially MMP-9 may play a role in the ECM remodeling process in patients with CCHD-SAH. TGF-Beta may counteract the MMP effect on the ECM remodeling process in patients with CCHD-SAH.

The usefulness of the exercise stress test to predict outcome in patients with chronic Chagas disease: a longitudinal cohort study.

BACKGROUND: Risk stratification is paramount for treatment of patients with chronic Chagas disease (CCD). The exercise stress test (EST) may be useful in the risk stratification of patients with this condition, but few studies have been performed in patients with CCD. METHODS: This was a longitudinal, retrospective cohort study. A total of 339 patients followed at our institution from January 2000 to December 2010 were screened. A total of 76 (22%) patients underwent the EST. The Cox proportional hazards model was used to identify independent predictors of all-cause mortality. RESULTS: Sixty-five (85%) patients were alive and 11 (14%) patients died by the study's close. In the univariate analysis, decreased systolic blood pressure (BP) at the peak of exercise and the double product were associated with all-cause mortality. However, in the multivariate analysis, only systolic BP at the peak of exercise was independently associated with all-cause mortality [hazard ratio 0.97 (95% confidence interval 0.94 to 0.99), p=0.02]. CONCLUSION: Systolic BP at the peak of EST is an independent predictor of mortality in patients with CCD.

Prevalence and clinical course of patients with chronic heart failure secondary to chronic Chagas heart disease associated with obstructive coronary artery disease.

BACKGROUND: The prevalence and the outcomes of patients with chronic Chagas heart disease with obstructive coronary artery disease (CCHD-CAD) and chronic heart failure (CHF) with precordial chest pain are unsettled. Accordingly, the aim of this study was to determine the prevalence and clinical course of patients with CHF secondary to CCHD-CAD. METHODS: Patients with positive serology for Chagas disease and systolic CHF were included; those with precordial chest pain and at least two risk factors for CAD underwent coronary arteriogram. RESULTS: In total 262 patients were included in the investigation; 234 (89%) had CHF secondary to CCHD alone, and 28 (11%) with CHF secondary to CCHD-CAD, as observed at coronary arteriogram. The survival probability of patients with CHF secondary to CCHD alone at 12, 24, 36, 48 and 72 mo was 79%, 64%, 54%, 44% and 33%, respectively, whereas survival probability for patients with CHF secondary to CCHD-CAD at 12, 24, 36, 48 and 72 mo was 96%, 80%, 71%, 66% and 57%, respectively (p=0.04). CONCLUSIONS: In patients with CCHD with CHF, the prevalence of CAD of 11% is not neglectable in those with precordial chest pain. The outcome for patients with precordial chest pain with CHF secondary to CCHD-CAD is better than that observed in patients with CHF secondary to CCHD alone.

Management of Cardiovascular Disease in Patients With COVID-19 and Chronic Chagas Disease: Implications to Prevent a Scourge Still Larger.

Cardiovascular diseases (CVD) are the most important cause of morbidity and mortality in the general population. Because the high prevalence of COVID-19 and chronic Chagas disease (CCD) where the latter is endemic, all such diseases will likely be observed in the same patient. While COVID-19 can provoke generalized endotheliitis, which can lead to a cytokine storm and a hyper-coagulable state culminating into in-site and at a distance thrombosis. Therefore, small-vessel coronary artery disease (CAD), cerebrovascular disease, thromboembolism, and arrhythmias are prominent findings in COVID-19. In CCD, small-vessel CAD, cardioembolic stroke, pulmonary embolism, heart failure and arrhythmias are frequently observed as a result of a similar but less intense mechanism. Consequently, the association of CCD and COVID-19 will likely increase the incidence of CVD. Thus, doctors on the frontline should be on the alert for this diagnostic possibility so that the proper treatment can be given without any delay.

Nonpharmaceutical public health interventions to curb the COVID-19 pandemic: a narrative review.

Nonpharmaceutical Interventions (NPI) consist of compulsory (isolation, quarantine, stay-at-home orders, banning public gatherings, nonessential business closures, school closures), and voluntary (social distancing, handwashing, respiratory etiquette, and universal mask wearing) measures. The aim of this narrative review is to evaluate the different forms of NPI and their effectiveness in combating the pandemic. Isolation can be indicated for symptomatic and asymptomatic infected people at home or at hospitals depending on the patient's clinical picture. Quarantine is a social distancing intervention in asymptomatic uninfected people who had contact with SARS-CoV-2 infected individuals. Stay-at-home orders refer to statewide mandates imposing nonessential business closures, prohibition of public events and gatherings, and travel restrictions. Studies have suggested that stay-at-home orders may be associated with a reduction in the incidence of COVID-19 in some countries. Mask wearing decreases the risk of COVID-19 in the community, especially when the surgical masks are used for vulnerable people. N-95 respirators protect health workers from COVID-19. NPI may be helpful to curb the COVID-19 pandemic while mass vaccination worldwide is not attainable, and the threat of SARS-COV-2 variants remain on the horizon.

Preventing heart failure: a position paper of the Heart Failure Association in collaboration with the European Association of Preventive Cardiology.

The heart failure epidemic is growing and its prevention, in order to reduce associated hospital readmission rates and its clinical and economic burden, is a key issue in modern cardiovascular medicine. The present consensus document aims to provide practical evidence-based information to support the implementation of effective preventive measures. After reviewing the most common risk factors, an overview of the population attributable risks in different continents is presented, to identify potentially effective opportunities for prevention and to inform preventive strategies. Finally, potential interventions that have been proposed and have been shown to be effective in preventing HF are listed.

Preventing heart failure: a position paper of the Heart Failure Association in collaboration with the European Association of Preventive Cardiology.

The heart failure epidemic is growing and its prevention, in order to reduce associated hospital readmission rates and its clinical and economic burden, is a key issue in modern cardiovascular medicine. The present position paper aims to provide practical evidence-based information to support the implementation of effective preventive measures. After reviewing the most common risk factors, an overview of the population attributable risks in different continents is presented, to identify potentially effective opportunities for prevention and to inform preventive strategies. Finally, potential interventions that have been proposed and have been shown to be effective in preventing heart failure are listed.

Does left ventricular reverse remodeling influence long-term outcomes in patients with Chagas cardiomyopathy?

BACKGROUND: The impact of left ventricular reverse remodeling (LVRR) on the prognosis of Chagas cardiomyopathy is unknown. The aim of this study was to determine whether the presence of LVRR can predict mortality in these patients. METHODS: From January 2000 to December 2010, the medical charts of 159 patients were reviewed. LVRR was defined as an increase of left ventricular ejection fraction (LVEF) and a decrease of left ventricular end-diastolic diameter (LVDD) by two-dimensional echocardiography. No patient underwent cardiac resynchronization therapy or required mechanical ventricular assistance. RESULTS: At baseline, median (25th-75th) LVDD was 64 mm (59-70), and median LVEF was 33.2% (26.4-40.1). LVRR was detected in 24.5% of patients in a 40-month (26-64) median follow-up. In the LVRR group, LVDD decreased from 64 mm (59-68) to 60 mm (56-65; p < 0.001), and LVEF increased from 31.3% (24.1-39.0) to 42.5% (32.2-47.7; p < 0.001). However, LVRR was not associated with heart failure hospitalization, cardiogenic shock, heart transplantation, or mortality (p > 0.05 for all comparisons). The Cox proportional hazard model analysis identified only cardiogenic shock (hazard ratio [HR]: 2.41; 95% confidence interval [CI]: 1.51-3.85; p < 0.001) and serum sodium level (HR: 0.91; 95% CI: 0.86-0.96; p < 0.001) as independent predictors of all-cause mortality. CONCLUSIONS: Left ventricular reverse remodeling occurs in one quarter of patients with Chagas cardiomyopathy and have no impact on the outcomes of patients with this condition.

MICA and KIR: Immunogenetic Factors Influencing Left Ventricular Systolic Dysfunction and Digestive Clinical Form of Chronic Chagas Disease.

Tissue damage observed in the clinical forms of chronic symptomatic Chagas disease seems to have a close relationship with the intensity of the inflammatory process. The objective of this study was to investigate whether the MICA (MHC class I-related chain A) and KIR (killer cell immunoglobulin-like receptors) polymorphisms are associated with the cardiac and digestive clinical forms of chronic Chagas disease. Possible influence of these genes polymorphisms on the left ventricular systolic dysfunction (LVSD) in patients with chronic Chagas heart disease was also evaluated. This study enrolled 185 patients with positive serology for Trypanosoma cruzi classified according to the clinical form of the disease: cardiac (n=107) and digestive (n=78). Subsequently, patients with the cardiac form of the disease were sub-classified as with LVSD (n=52) and without LVSD (n=55). A control group was formed of 110 healthy individuals. Genotyping was performed by polymerase chain reaction-sequence specific oligonucleotide probes (PCR-SSOP). Statistical analyzes were carried out using the Chi-square test and odds ratio with 95% confidence interval was also calculated to evaluate the risk association. MICA-129 allele with high affinity for the NKG2D receptor was associated to the LVSD in patients with CCHD. The haplotype MICA*008~HLA-C*06 and the KIR2DS2-/KIR2DL2-/KIR2DL3+/C1+ combination were associated to the digestive clinical form of the disease. Our data showed that the MICA and KIR polymorphisms may exert a role in the LVSD of cardiac patients, and in digestive form of Chagas disease.

Noninvasive prediction of late potentials in the signal-averaged ECG in patients with chronic Chagas disease.

INTRODUCTION: Considering the importance of ventricular arrhythmias in the prediction of sudden cardiac death in chronic Chagas heart disease, the aim of the present study was to associate late potentials observed in the signal-averaged electrocardiogram (SAECG) with either non-sustained ventricular tachycardia in the 24-hour Holter monitoring or reduced left ventricular ejection fraction in the 2-dimension echocardiogram. METHODS: This was a retrospective transversal study. The medical charts of 49 patients with chronic Chagas heart disease that underwent 24-hour Holter monitoring at our institution from September 2012 to December 2015 were reviewed. In the univariate analysis, variables associated with SAECG at a p value <0.05 were entered a multivariate stepwise logistic regression analysis through the model forward. A p value <0.05 was considered to have statistical significance. RESULTS: In the univariate analysis, right bundle branch block, left atrial diameter, left ventricular systolic diameter, and left ventricular ejection fraction were associated with late potential in the SAECG. In the multivariate analysis, however, right bundle branch block and left atrial diameter were retained as independent predictors of late potentials in the SAECG. CONCLUSIONS: Neither ventricular arrhythmias in the 24-Holter monitoring nor reduced left ventricular ejection fraction in the 2-D echocardiogram were associated with late potentials in the SAECG of patients with chronic Chagas heart disease.

Pharmacological Treatment of Patients with Mild to Moderate COVID-19: A Comprehensive Review.

Mild to moderate COVID-19 can be found in about 80% of patients. Although mortality is low, mild to moderate COVID-19 may progress to severe or even critical stages in about one week. This poses a substantial burden on the health care system, and ultimately culminates in death or incapacitation and hospitalization. Therefore, pharmacological treatment is paramount for patients with this condition, especially those with recognized risk factors to disease progression. We conducted a comprehensive review in the medical literature searching for randomized studies carried out in patients with mild to moderate COVID-19. A total of 14 randomized studies were identified, enrolling a total of 6848 patients. Nine studies (64%) were randomized, placebo-controlled trials, whereas five were open-label randomized trials (35%). We observed that Bamlanivimab and nitazoxanide reduced viral load, whereas ivermectin may have shortened time to viral clearance; Interferon Beta-1 reduced time to viral clearance and vitamin D reduced viral load; Favirapir, peginterferon, and levamisole improved clinical symptoms, whereas fluvoxamine halted disease progression; inhaled budesonide reduced the number of hospitalizations and visits to emergency departments; colchicine reduced the number of deaths and hospitalizations. Collectively, therefore, these findings show that treatment of early COVID-19 may be associated with reduced viral load, thus potentially decreasing disease spread in the community. Moreover, treatment of patients with mild to moderate COVID-19 may also be associated with improved clinical symptoms, hospitalization, and disease progression. We suggest that colchicine, inhaled budesonide, and nitazoxanide, along with nonpharmacological measures, based on efficacy and costs, may be used to mitigate the effects of the COVID-19 pandemic in middle-income countries.