Search results for: cardiac tumour

Authors: Birgit Rasmussen, Thomas Maribo, Bente S. Toft

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BACKGROUND: Cardiac rehabilitation is the standard treatment for ischemic heart disease. Cardiac rehabilitation improves quality of life, reduces mortality and the risk of readmission, and provides patients with valuable knowledge and encouragement from peers and staff. Still, less than half of eligible patients enroll. Face-to-face interventions have the potential to support patients' decision-making and increase enrolment in cardiac rehabilitation. However, we lack knowledge of the content and characteristics of interventions. AIM: The aim was to outline and evaluate the content and characteristics of studies that have reported on face-to-face interventions to encourage enrolment in cardiac rehabilitation in patients with ischemic heart disease. METHOD: This scoping review followed the Joanne Briggs Institute methodology. Based on an a-priori protocol that defined the systematic search criteria, six databases were searched for studies published between 2001 and 2023. Two reviewers independently screened and selected studies. All authors discussed the summarized data prior to the narrative presentation. RESULTS: After screening and full text review of 5583 records, 20 studies of heterogeneous design and content were included. Four studies described the key contents in face-to-face interventions to be education, support of autonomy, addressing reasons for change, and emotional and cognitive support while showing understanding. Two studies used motivational interviewing to target patients' experiences and address worries and anticipated difficulties. Four quantitative studies found associations between enrolment and intention to attend, cardiac rehabilitation barriers, exercise self-efficacy, and perceived control. When patients asked questions, enrolment rates were higher, while providing reassurance and optimism could lead to non-attendance if patients had a high degree of worry. In qualitative studies, support to overcome barriers and knowledge about health benefits from participation in cardiac rehabilitation facilitated enrolment. Feeling reassured that the cardiac condition was good could lead to non-attendance. DISCUSSION AND CONCLUSION: To support patients' enrolment in cardiac rehabilitation, it is recommended that interventions integrate a person-centered dialogue. Individual worries and barriers to cardiac rehabilitation should be jointly explored. When talking with patients for whom worries predominate, the recommendation is to focus on the patients' perspectives and avoid too much focus on reassurance and problem-solving. The patients' perspectives, the mechanisms of change, and the process evaluation of the intervention including person-centeredness are relevant to include in future studies.

Keywords: ischemic heart disease, cardiac rehabilitation, enrolment, person-centered, in-hospital interventions

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Authors: Heru Al Amin

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Sarcoidosis is a granulomatous inflammatory disorder of unclear etiology that can affect multiple different organ systems. Isolated cardiac sarcoidosis is a very rare condition that causes lethal arrhythmia and heart failure. A definite diagnosis of cardiac sarcoidosis remains challenging. The use of multimodality imaging plays a pivotal role in the diagnosis of this entity. Case summary: In this report, we discuss a case of a 50-year-old woman who presented with recurrent palpitation, dizziness, vertigo and presyncope. Electrocardiogram revealed variable heart blocks, including first-degree AV block, second-degree AV block, high-degree AV block, complete AV block, trifascicular block and sometimes supraventricular arrhythmia. Twenty-four hours of Holter monitoring show atrial bigeminy, first-degree AV block and trifascicular block. Transthoracic echocardiography showed Thinning of basal anteroseptal and inferred septum with LV dilatation with reduction of Global Longitudinal Strain. A dual-chamber pacemaker was implanted. CT Coronary angiogram showed no coronary artery disease. Cardiac magnetic resonance revealed basal anteroseptal and inferior septum thinning with focal edema with LGE suggestive of sarcoidosis. Computed tomography of the chest showed no lymphadenopathy or pulmonary infiltration. 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) of the whole body showed. We started steroids and followed up with the patient. Conclusion: This case serves to highlight the challenges in identifying and managing isolated CS in a young patient with recurrent syncope with variable heart block. Early, even late initiation of steroids can improve arrhythmia as well as left ventricular function.

Keywords: cardiac sarcoidosis, conduction abnormality, syncope, cardiac MRI

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Authors: Kapoor Anurag, Sharma Pradeep, Mittal K Kailash, Kumar Ajai, Jawad Kalbe, Amit Kumar Singh

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Background: Oral squamous cell carcinoma (OSCC) is the most prevalent malignant tumour on a global scale. Limited research has been conducted on tumour markers in oral cancer, and additional evaluation is required for several tumour producers that show clinical promise. The present study aimed to find out the co-relation of β-2 Microglobulin and Lipid Bound Sialic Acid in oral carcinoma patients. Methodology: The present case-control study was carried out on 35 patients with histopathologically confirmed OSCC and 35 age-matched controls. Serum concentrations of 2-Microglobulin and Total Sialic Acid (TSA) in the participants were determined via ELISA and spectrophotometric technique, respectively. Results: The OSCC group consisted of 20 males and 15 females, with an average age of 58 years, while the control group comprised 18 males and 17 females, with an average age of 55 years. Elevated levels of β2-microglobulin (3.87±0.12) and LSA (73.57±2.42) were observed in OSCC patients compared to controls (2.25±0.18; 65.21±2.06, respectively). Further examination based on smoking status revealed a significant increase in both β2-microglobulin and LSA levels among smokers compared to non-smokers (p < 0.05). Conclusion: The study suggests a notable association between higher levels of β2-microglobulin and LSA in oral squamous cell carcinoma (OSCC) patients who smoke compared to non-smokers. This observation leads to a hypothesis that this disparity could potentially serve as a significant contributing factor to the advancement of oral cancer.

Keywords: biochemistry human cancer, human, oral carcinoma, marker

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Authors: Ioannis Panagiotopoulos, Efstathios Kastritis, Anastasia Katinioti, Georgios Efthymiadis, Argyrios Doumas, Maria Koutelou

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Introduction: Transthyretin amyloidosis (ATTR) is a rare but serious infiltrative disease. Myocardial scintigraphy with DPD has emerged as the most effective, non-invasive, highly sensitive, and highly specific diagnostic method for cardiac ATTR amyloidosis. However, there are cases in which additional laboratory investigations reveal AL amyloidosis or other diseases despite a positive DPD scintigraphy. We describe the experience from the Onassis Cardiac Surgery Center and the monitoring center for infiltrative myocardial diseases of the cardiology clinic at AHEPA. Materials and Methods: All patients with clinical suspicion of cardiac or extracardiac amyloidosis undergo a myocardial scintigraphy scan with Tc-99m DPD. In this way, over 500 patients have been examined. Further diagnostic approach based on clinical and imaging findings includes laboratory investigation and invasive techniques (e.g., biopsy). Results: Out of 76 patients in total with positive myocardial scintigraphy Grade 2 or 3 according to the Perugini scale, 8 were proven to suffer from AL Amyloidosis during the investigation of paraproteinemia. Among these patients, 3 showed Grade 3 uptake, while the rest were graded as Grade 2, or 2 to 3. Additionally, one patient presented diffuse and unusual radiopharmaceutical uptake in soft tissues throughout the body without cardiac involvement. These findings raised suspicions, leading to the analysis of κ and λ light chains in the serum, as well as immunostaining of proteins in the serum and urine of these specific patients. The final diagnosis was AL amyloidosis. Conclusion: The value of DPD scintigraphy in the diagnosis of cardiac amyloidosis from transthyretin is undisputed. However, positive myocardial scintigraphy with DPD should not automatically lead to the diagnosis of ATTR amyloidosis. Laboratory differentiation between ATTR and AL amyloidosis is crucial, as both prognosis and therapeutic strategy are dramatically altered. Laboratory exclusion of paraproteinemia is a necessary and essential step in the diagnostic algorithm of ATTR amyloidosis for all positive myocardial scintigraphy with diphosphonate tracers since >20% of patients with Grade 3 and 2 uptake may conceal AL amyloidosis.

Keywords: AL amyloidosis, amyloidosis, ATTR, myocardial scintigraphy, Tc-99m DPD

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Authors: Sandipika Gupta

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Objective: Due to admirably low 30-day mortality rates for paediatric cardiac surgery, it is now pertinent to turn towards more intermediate-length outcomes such as morbidities closely associated with these surgeries. One such morbidity, major adverse events (MAE) comprises a group of adverse outcomes associated with paediatric cardiac surgery (e.g. cardiac arrest, major haemorrhage). Methods: This is a retrospective study that analysed the incidence and impact of MAE which was the primary outcome in the UK population. The data was collected in 5 centres between October 2015 and June 2017, amassing 3090 surgical episodes. The incidence and risk factors for MAE, were assessed through descriptive statistical analyses and multivariate logistic regression. The secondary outcomes of life status at 6 months and the length of hospital stay were also evaluated to understand the impact of MAE on patients. Results: Out of 3090 episodes, 134 (4.3%) had a postoperative MAE. The majority of the episodes were in: neonates (47%, P<0.001), high-risk cardiac diagnosis groups (20.1%, P<0.001), episodes with longer 5mes on the bypass (72.4%, P<0.001) and urgent surgeries (57.9%, P<0.001). Episodes reporting MAE also reported longer lengths of stay in hospital (29 days vs 9 days, P<0.001). Furthermore, patients experiencing MAE were at a higher risk of mortality at the 6-month life status check (mortality rates: 29.2% vs 2%, P<0.001).Conclusions: Key risk factors were identified. An important negative impact of MAE was found for patients. The identified risk factors could be used to profile and flag at-risk patients. Monitoring of MAE rates and closer investigation into the care pathway before and after individual MAEs in children’s heart units may lead to a reduction in these terrible events.

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Authors: L. Bikulciene, E. Venskaityte, G. Jarusevicius

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Non-stationary and nonlinear signals generated by living complex systems defy traditional mechanistic approaches, which are based on homeostasis. Previous our studies have shown that the evaluation of the interactions of physiological signals by using special analysis methods is suitable for observation of physiological processes. It is demonstrated the possibility of using deep physiological model, based interpretation of the changes of the human body’s functional states combined with an application of the analytical method based on matrix theory for the physiological signals analysis, which was applied on high risk cardiac patients. It is shown that evaluation of cardiac signals interactions show peculiar for each individual functional changes at the onset of hemodynamic restoration procedure. Therefore we suggest that the alterations of functional state of the body, after patients overcome surgery can be complemented by the data received from the suggested approach of the evaluation of functional variables interactions.

Keywords: cardiac diseases, complex systems theory, ECG analysis, matrix analysis

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Authors: Fahad Almehmadi, Abdullah Alrajhi, Bader K. Alaslab, Abdullah A. Al Qurashi, Hattan A. Hassani

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Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy (ARVD/C) is an uncommon, inheritable cardiac disorder characterized by the progressive substitution of cardiac myocytes by fibro-fatty tissues. This pathologic substitution predisposes patients to ventricular arrhythmias and right ventricular failure. The underlying genetic defect predominantly involves genes encoding for desmosome proteins, particularly plakophilin-2 (PKP2). These aberrations lead to impaired cell adhesion, heightening the susceptibility to fibrofatty scarring under conditions of mechanical stress. Primarily, ARVD/C affects the right ventricle, but it can also compromise the left ventricle, potentially leading to biventricular heart failure. Clinical presentations can vary, spanning from asymptomatic individuals to those experiencing palpitations, syncopal episodes, and, in severe instances, sudden cardiac death. The establishment of a diagnostic criterion specifically tailored for ARVD/C significantly aids in its accurate diagnosis. Nevertheless, the task of early diagnosis is complicated by the disease's frequently asymptomatic initial stages, and the overall rarity of ARVD/C cases reported globally. In some cases, as exemplified by the adult female patient in this report, the disease may advance to terminal stages, rendering therapies like Ventricular Tachycardia (VT) ablation ineffective. This case underlines the necessity for increased awareness and understanding of ARVD/C to aid in its early detection and management. Through such efforts, we aim to decrease morbidity and mortality associated with this challenging cardiac disorder.

Keywords: ARVD/C, cardiology, interventional cardiology, cardiac electrophysiology

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Authors: Ratna Farida Soenarto, Anas Alatas, Made Ryan Kharmayani

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Background: Conventional ultrafiltration (CUF) system was shown to be helpful in reducing anti-inflammatory mediators for patients who underwent open heart surgery. Additionally, modified ultrafiltration (MUF) has been shown to reduce anti-inflammatory mediators further while reducing interstitial fluid volume at the same time. However, there has been minimal data concerning the efficacy of combining both ultrafiltration methods. This study aims to compare inflammation marker, vascular resistance, and cardiac index on CUF+MUF patients with CUF only patients undergoing open heart surgery. Method: This is a single blind randomized controlled trial on patients undergoing open heart surgery between June 2021 - October 2021 in CiptoMangunkusumo National Referral Hospital and Jakarta Heart Hospital. Patients wererandomized using block randomization into modified ultrafiltration following conventional ultrafiltration (CUF+MUF) and conventional ultrafiltration (CUF) only. Outcome assessed in this study were 24-hoursinterleukin-6 levels, systemic vascular resistance (SVR), pulmonary vascular resistance (PVR), and cardiac index. Results: A total of 38patients were included (19 CUF+MUF and 19 CUF subjects). There was no difference in postoperative IL-6 level between groups (p > 0.05).No difference in PVR was observed between groups.Higher difference in SVR was observed in CUF+MUF group (-646 vs. -261dyn/s/cm-5, p < 0.05). Higher cardiac index was observed on CUF+MUF group (0.93 vs. 0.48, p < 0.05). Conclusion: Patients undergoing open heart surgery with modified ultrafiltration following conventional ultrafiltration had similar systemic inflammatory response and better cardiac response than those having conventional ultrafiltration.

Keywords: open-heart, CUF, MUF, SVR, PVR, IL-6

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Authors: Kh. Dehkordi, R. Sharifi Gholam, S. Arshadi

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Objective: Oxidative stress is produced under diabetic conditions and possibly causes various forms of tissue damage inpatients with diabetes. Antioxidants defend against the harmful effect of free radicals, which are associated with heart disease, cancer, arthritis, aging and many other diseases1). Antioxidants are very stable molecules capable of neutralizing free radicals by donating an electron to them.The aim of this study was to examine the effect of swimming training, fenugreek seed extract and glibenclamide on plasma glucose and cardiac antioxidants activity in diabetic rats. Design: For this purpose, fifty male wistar rats were divided into five groups, two groups of control rats (diabetic control [DC] and healthy control [HC]), one group of endurance swimming training (EST), one group of fenugreek seed extract highdose (F1, 1.74 g/kg b.w), one group of fenugreek seed extract middle dose (F2, 0.87 g/kg b.w), one group of glibenclamide (G, 0.5 mg/kg b.w). Materials and Methods: Diabetes induced by streptozotocine (STZ), data was analyzed using the one-way ANOVA followed by a Tukey test. Significance level was 0.05. Results: All of the groups' exception of HC showed significant decrease in body weight (P < 0.05), but the diabetic control and swimming training group exhibited a more decrease. All of the groups have shown a significant decrease in plasma glucose than DC group (P < 0.05) but this reduction was more in G group than DC no HC group. S, G and HC groups have shown significant increase in cardiac antioxidant than DC group (P < 0.05) but there wasn't significant difference in other groups (P > 0.05). Conclusion: The present results indicate that regular swimming training lead to decrease in plasma glucose and enhanced cardiac antioxidants in diabetic rats.

Keywords: swimming, glucose, cardiac, antioxidants

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Authors: Daniel F. Bohorquez, Luis M. Agudelo, Henry H. León

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Heart rate variability (HRV) is defined as the temporary variation between heartbeats or RR intervals (distance between R waves in an electrocardiographic signal). This distance is currently a recognized biomarker. With the analysis of the distance, it is possible to assess the sympathetic and parasympathetic nervous systems. These systems are responsible for the regulation of the cardiac muscle. The analysis allows health specialists and researchers to diagnose various pathologies based on this variation. For the acquisition and analysis of HRV taken from a cardiac electrical signal, electronic equipment and analysis software that work independently are currently used. This complicates and delays the process of interpretation and diagnosis. With this delay, the health condition of patients can be put at greater risk. This can lead to an untimely treatment. This document presents a single portable device capable of acquiring electrocardiographic signals and calculating a total of 19 HRV metrics. This reduces the time required, resulting in a timelier intervention. The device has an electrocardiographic signal acquisition card attached to a microcontroller capable of transmitting the cardiac signal wirelessly to a mobile device. In addition, a mobile application was designed to analyze the cardiac waveform. The device calculates the RR and different metrics. The application allows a user to visualize in real-time the cardiac signal and the 19 metrics. The information is exported to a cloud database for remote analysis. The study was performed under controlled conditions in the simulated hospital of the Universidad de la Sabana, Colombia. A total of 60 signals were acquired and analyzed. The device was compared against two reference systems. The results show a strong level of correlation (r > 0.95, p < 0.05) between the 19 metrics compared. Therefore, the use of the portable system evaluated in clinical scenarios controlled by medical specialists and researchers is recommended for the evaluation of the condition of the cardiac system.

Keywords: biological signal análisis, heart rate variability (HRV), HRV metrics, mobile app, portable device.

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Authors: H. Booke, R. Nordmeier

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Sudden cardiac arrest is sometimes eye-witnessed by kids. Mostly, their (grand-)parents are affected by sudden cardiac arrest, putting these kids under enormous psychological pressure: Although they are more than desperate to help, they feel insecure and helpless and are afraid of causing harm rather than realizing their chance to help. Even years later, they may blame themselves for not having helped their beloved ones. However, the absolute majority of school children - at least in Germany - is not educated to provide first aid. Teaching young kids (5th grade) in basic life support thus may help to save lives while washing away the kids' fear from causing harm during cardio-pulmonary resuscitation. A teaching of circulatory and respiratory (patho-)physiology, followed by hands-on training of basic life support for every single child, was offered to each school in our district. The teaching was performed by anesthesiologists, and the program was called 'kids can save lives'. However, before enrollment in this program, the entire class must have had lessons in biology with a special focus on heart and circulation as well as lung and gas exchange. More than 1.000 kids were taught and trained in basic life support, giving them the knowledge and skills to provide basic life support. This may help to reduce the rate of failure to provide first aid. Therefore, educating young kids in basic life support may not only help to save lives, but it also may help to prevent any feelings of guilt because of not having helped in cases of eye-witnessed sudden cardiac arrest.

Keywords: teaching, children, basic life support, cardiac arrest, CPR

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Authors: Awad G. Abdellatif, Huda M. Gargoum, Abdelkader A. Debani, Mudafara Bengleil, Salmin Alshalmani, N. El Zuki, Omran El Fitouri

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In this study, the administration of 660 mg/kg of the ethanolic extract of the Alhgigraecorum (camel thorn) to mice, showed a significant decrease in the level of transaminases in animals treated with a combination of CTE plus carbon tetrachloride (CCl4) or acetaminophen as compared to animals receiving CCl4 or acetaminophen alone. The histopathological investigation also confirmed that camel thorn extract protects the liver against damage-induced either by carbon tetrachloride or acetaminophen. On the other hand, the cardiac toxicity produced by adriamycin was significantly increased in the presence of the ethanolic extract of camel thorn. Our study suggested that camel thorn can protect the liver against the injury produced by carbon tetrachloride or acetaminophen, with an unexpected increase in the cardiac toxicity–induced by adriamycin in rodents.

Keywords: ethanolic, alhgigraecorum, tetrachloride, acetaminophen

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Authors: Visith Siriphuwanun, Yodying Punjasawadwong, Suwinai Saengyo, Kittipan Rerkasem

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Objective: To determine incidences and factors associated with perioperative cardiac arrest in trauma patients who received anesthesia for emergency surgery. Design and setting: Retrospective cohort study in trauma patients during anesthesia for emergency surgery at a university hospital in northern Thailand country. Patients and methods: This study was permitted by the medical ethical committee, Faculty of Medicine at Maharaj Nakorn Chiang Mai Hospital, Thailand. We clarified data of 19,683 trauma patients receiving anesthesia within a decade between January 2007 to March 2016. The data analyzed patient characteristics, traumas surgery procedures, anesthesia information such as ASA physical status classification, anesthesia techniques, anesthetic drugs, location of anesthesia performed, and cardiac arrest outcomes. This study excluded the data of trauma patients who had received local anesthesia by surgeons or monitoring anesthesia care (MAC) and the patient which missing more information. The factor associated with perioperative cardiac arrest was identified with univariate analyses. Multiple regressions model for risk ratio (RR) and 95% confidence intervals (CI) were used to conduct factors correlated with perioperative cardiac arrest. The multicollinearity of all variables was examined by bivariate correlation matrix. A stepwise algorithm was chosen at a p-value less than 0.02 was selected to further multivariate analysis. A P-value of less than 0.05 was concluded as statistically significant. Measurements and results: The occurrence of perioperative cardiac arrest in trauma patients receiving anesthesia for emergency surgery was 170.04 per 10,000 cases. Factors associated with perioperative cardiac arrest in trauma patients were age being more than 65 years (RR=1.41, CI=1.02–1.96, p=0.039), ASA physical status 3 or higher (RR=4.19–21.58, p < 0.001), sites of surgery (intracranial, intrathoracic, upper intra-abdominal, and major vascular, each p < 0.001), cardiopulmonary comorbidities (RR=1.55, CI=1.10–2.17, p < 0.012), hemodynamic instability with shock prior to receiving anesthesia (RR=1.60, CI=1.21–2.11, p < 0.001) , special techniques for surgery such as cardiopulmonary bypass (CPB) and hypotensive techniques (RR=5.55, CI=2.01–15.36, p=0.001; RR=6.24, CI=2.21–17.58, p=0.001, respectively), and patients who had a history of being alcoholic (RR=5.27, CI=4.09–6.79, p < 0.001). Conclusion: Incidence of perioperative cardiac arrest in trauma patients receiving anesthesia for emergency surgery was very high and correlated with many factors, especially age of patient and cardiopulmonary comorbidities, patient having a history of alcoholic addiction, increasing ASA physical status, preoperative shock, special techniques for surgery, and sites of surgery including brain, thorax, abdomen, and major vascular region. Anesthesiologists and multidisciplinary teams in pre- and perioperative periods should remain alert for warning signs of pre-cardiac arrest and be quick to manage the high-risk group of surgical trauma patients. Furthermore, a healthcare policy should be promoted for protecting against accidents in high-risk groups of the population as well.

Keywords: perioperative cardiac arrest, trauma patients, emergency surgery, anesthesia, factors risk, incidence

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Authors: Leonardo Juan Ramírez López, Javier Oswaldo Rodriguez Velasquez

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We have designed a Holter that measures the heart´s activity for over 24 hours, implemented a prediction methodology, and generate alarms as well as indicators to patients and treating physicians. Various diagnostic advances have been developed in clinical cardiology thanks to Holter implementation; however, their interpretation has largely been conditioned to clinical analysis and measurements adjusted to diverse population characteristics, thus turning it into a subjective examination. This, however, requires vast population studies to be validated that, in turn, have not achieved the ultimate goal: mortality prediction. Given this context, our Insight Research Group developed a mathematical methodology that assesses cardiac dynamics through entropy and probability, creating a numerical and geometrical attractor which allows quantifying the normalcy of chronic and acute disease as well as the evolution between such states, and our Tigum Research Group developed a holter device with 12 channels and advanced computer software. This has been shown in different contexts with 100% sensitivity and specificity results.

Keywords: attractor , cardiac, entropy, holter, mathematical , prediction

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Authors: Rekaya A. Shabbir, Marco Mingarelli, Glenn Flux, Ananya Choudhury, Tim A. D. Smith

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Introduction: Heterogeneity of dose distributions across a tumour is problematic for targeted radiotherapy. Gold nanoparticles (AuNPs) enhance dose-distributions of targeted radionuclides. The aim of this study is to demonstrate if tumour dose-distribution of targeted AuNPs radiolabelled with either of two radioisotopes (¹⁷⁷Lu and ⁹⁰Y) in breast cancer cells produced homogeneous dose distributions. Moreover, in vitro and in vivo studies were conducted to study the importance of receptor level on cytotoxicity of EGFR-targeted AuNPs in breast and colorectal cancer cells. Methods: AuNPs were functionalised with DOTA and OPPS-PEG-SVA to optimise labelling with radionuclide tracers and targeting with Erbitux. Radionuclides were chelated with DOTA, and the uptake of the radiolabelled AuNPs and targeted activity in vitro in both cell lines measured using liquid scintillation counting. Cells with medium (HCT8) and high (MDA-MB-468) EGFR expression were incubated with targeted ¹⁷⁷Lu-AuNPs for 4h, then washed and allowed to form colonies. Nude mice bearing tumours were used to study the biodistribution by injecting ¹⁷⁷Lu-AuNPs or ⁹⁰Y-AuNPs via the tail vein. Heterogeneity of dose-distribution in tumours was determined using autoradiography. Results: Colony formation (% control) was 81 ± 4.7% (HCT8) and 32 ± 9% (MDA-MB-468). High uptake was observed in the liver and spleen, indicating hepatobiliary excretion. Imaging showed heterogeneity in dose-distributions for both radionuclides across the tumours. Conclusion: The cytotoxic effect of EGFR-targeted AuNPs is greater in cells with higher EGFR expression. Dose-distributions for individual radiolabelled nanoparticles were heterogeneous across tumours. Further strategies are required to improve the uniformity of dose distribution prior to clinical trials.

Keywords: cancer cells, dose distributions, radionuclide therapy, targeted gold nanoparticles

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Authors: Lingxia Li, Frédéric Schnell, Shuzhe Ding, Solène Le Douairon Lahaye

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Background: The risk of sudden cardiac arret/death (SCA/D) in athletes is controversial. There is a lack of meta-analyses assessing the sex differences in the risk of SCA/D in competitive athletes. Purpose: The aim of the present study was to evaluate sex differences in the incidence of SCA/D in competitive athletes using meta-analyses. Methods: The systematic review was registered in the PROSPERO database (registration ID: CRD42023432022) and was conducted according to the PRISMA guidelines. PubMed, Embase, Scopus, SPORT Discus and Cochrane Library were searched up to July 2023. To avoid systematic bias in data pooling, only studies with data for both sexes were included. Results: From the 18 included studies, 2028 cases of SCA/D were observed (males 1821 (89.79%), females 207 (10.21%)). The age ranges from the adolescents (<26 years) to the elderly (>45 years). The incidence in male athletes was 1.32/100,000 AY (95% CI: [0.90, 1.93]) and in females was 0.26/100,000 AY (95% CI: [0.16, 0.43]), the incidence rate ratio (IRR) was 6.43 (95% CI: [4.22, 9.79]). The subgroup synthesis showed a higher incidence in males than in females in both age groups <25 years and ≤35 years, the IRR was 5.86 (95% CI: [4.69, 7.32]) and 5.79 (95% CI: [4.73, 7.09]), respectively. When considering the events, the IRR was 6.73 (95%CI: [3.06, 14.78]) among studies involving both SCA/D events and 7.16 (95% CI: [4.93, 10.40]) among studies including only cases of SCD. The available clinical evidence showed that cardiac events were most frequently seen in long-distance running races (26, 35.1%), marathon (16, 21.6%) and soccer (10, 13.5%). Coronary artery disease (14, 18.9%), hypertrophic cardiomyopathy (8, 10.8%), and arrhythmogenic right ventricular cardiomyopathy (7, 9.5%) are the most common causes of SCA/D in competitive athletes. Conclusion: The meta-analysis provides evidence of sex differences in the incidence of SCA/D in competitive athletes. The incidence of SCA/D in male athletes was 6 to 7 times higher than in females. Identifying the reasons for this difference may have implications for targeted the prevention of fatal evets in athletes.

Keywords: incidence, sudden cardiac arrest, sudden cardiac death, sex difference, athletes

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Authors: Sergey Kholodkevich, Tatiana Kuznetsova

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The objective assessment of ecological state of water ecosystems is impossible without the use of biological methods of the environmental monitoring capable in the integrated look to reveal negative for biota changes of quality of water as habitats. Considerable interest for the development of such methods of environmental quality control represents biomarker approach. Measuring systems, by means of which register cardiac activity characteristics, received the name of bioelectronic. Bioelectronic systems are information and measuring systems in which animals (namely, benthic invertebrates) are directly included in structure of primary converters, being an integral part of electronic system of registration of these or those physiological or behavioural biomarkers. As physiological biomarkers various characteristics of cardiac activity of selected invertebrates have been used in bioelectronic system.lChanges in cardiac activity are considered as integrative measures of the physiological condition of organisms, which reflect the state of the environment of their dwelling. Greatest successes in the development of tools of biological methods and technologies of an assessment of surface water quality in real time. Essential advantage of bioindication of water quality by such tool is a possibility of an integrated assessment of biological effects of pollution on biota and also the expressness of such method and used approaches. In the report the practical experience of authors in biomonitoring and bioindication of an ecological condition of sea, brackish- and freshwater areas is discussed. Authors note that the method of non-invasive cardiac activity monitoring of selected invertebrates can be used not only for the advancement of biomonitoring, but also is useful in decision of general problems of comparative physiology of the invertebrates.

Keywords: benthic invertebrates, physiological state, heart rate monitoring, water quality assessment

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Authors: Helan Satish, M. Ramasubba Reddy

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The simulation of an endocardial cell for gene mutation in the cardiac sodium ion channel NaV1.5, encoded by SCN5A gene, is discussed. The characterization of Brugada Syndrome by loss of function effect on SCN5A mutation due to L812Q mutant present in the DII-S4 transmembrane region of the NaV1.5 channel protein and its effect in an endocardial cell is studied. Ten Tusscher model of human ventricular action potential is modified to incorporate the changes contributed by L812Q mutant in the endocardial cells. Results show that BrS-associated SCN5A mutation causes reduction in the inward sodium current by modifications in the channel gating dynamics such as delayed activation, enhanced inactivation, and slowed recovery from inactivation in the endocardial cell. A decrease in the inward sodium current was also observed, which affects depolarization phase (Phase 0) that leads to reduction in the spike amplitude of the cardiac action potential.

Keywords: SCN5A gene mutation, sodium channel, Brugada syndrome, cardiac arrhythmia, action potential

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Authors: Hyun Chang Kim, Yong Hun Jung, Kyung Woon Jeung

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Background: From the viewpoint of cardiac pump theory, the area of the left ventricle (LV) subjected to compression increases as the LV lies closer to the sternum, possibly resulting in higher blood flow in patients with LV closer to the sternum. However, no study has evaluated LV position during cardiac arrest or its relationship with hemodynamic parameters during cardiopulmonary resuscitation (CPR). The objectives of this study were to determine whether the position of the LV relative to the anterior-posterior axis representing the direction of chest compression shifts during cardiac arrest and to examine the relationship between LV position and hemodynamic parameters during CPR. Methods: Subcostal view echocardiograms were obtained from 15 pigs with the transducer parallel to the long axis of the sternum before inducing ventricular fibrillation (VF) and during cardiac arrest. Computed tomography was performed in three pigs to objectively observe LV position during cardiac arrest. LV position parameters including the shortest distance between the anterior-posterior axis and the mid-point of the LV chamber (DAP-MidLV), the shortest distance between the anterior-posterior axis and the LV apex (DAP-Apex), and the area fraction of the LV located on the right side of the anterior-posterior axis (LVARight/LVATotal) were measured. Results: DAP-MidLV, DAP-Apex, and LVARight/LVATotal decreased progressively during untreated VF and basic life support (BLS), and then increased during advanced cardiovascular life support (ACLS). A repeated measures analysis of variance revealed significant time effects for these parameters. During BLS, the end-tidal carbon dioxide and systolic right atrial pressure were significantly correlated with the LV position parameters. During ACLS, systolic arterial pressure and systolic right atrial pressure were significantly correlated with DAP-MidLV and DAP-Apex. Conclusions: LV position changed significantly during cardiac arrest compared to the pre-arrest baseline. LV position during CPR had significant correlations with hemodynamic parameters.

Keywords: heart arrest, cardiopulmonary resuscitation, heart ventricle, hemodynamics

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Authors: Fahad Raj Khan, Suleman Khan

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There is a lack of consensus about the predictive value of raised blood glucose levels in terms of major adverse cardiac events (MACEs) in non-diabetic patients admitted for acute decompensated heart failure. The purpose of this research was to examine the long-term prognosis of acute decompensated heart failure (ADHF) in non-diabetic persons who had increased blood glucose levels, i.e., stress hyperglycemia, at the time of their ADHF hospitalization. The research involved 650 non-diabetic patients. Based on their admission stress hyperglycemia, they were divided into two groups.ie with and without (SHGL). The two groups' one-year outcomes for major adverse cardiac events (MACEs) were compared, and key predictors of MACEs were discovered. For statistical analysis, the two-tailed Mann-Whitney U test, Fisher's exact test, and binary logistic regression analysis were utilized. SHGL was found in 353 (54.3%) individuals. It was more frequent in men than in women. About 27% of patients with SHGL had previously been admitted for ADHF. Almost 62% were hypertensive, whereas 14 % had CKD. MACEs were significantly predicted by SHGL, HTN, prior hospitalization for ADHF, CKD, and cardiogenic shock upon admission. SHGL at the time of ADHF admission, independent of DM status, may be a predictive indication of MACEs.

Keywords: stress hyperglycemia, acute heart failure, major adverse cardiac events, MACEs

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Authors: Slawomir Pilip, Michal Wasilewski, Daniel Celinski, Leszek Szpakowski, Grzegorz Michalak

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The aim of the study was to evaluate the effectiveness of cardiopulmonary resuscitation taken by Medical Emergency Teams (MET) at the place of an accident including the usage of mechanical chest compression systems. In the period of January-May 2017, there were 137 cases of a sudden cardiac arrest in a chosen region of Eastern Poland with 360.000 inhabitants. Medical records and questionnaires filled by METs were analysed to prove the effectiveness of cardiopulmonary resuscitations that were considered to be effective when an early indication of spontaneous circulation was provided and the patient was taken to hospital. A chest compression system used by METs was applied in 60 cases (Lucas3 - 34 patients; Auto Pulse - 24 patients). The effectiveness of cardiopulmonary resuscitation among patients who were employed a chest compression system was much higher (43,3%) than the manual cardiac massage (36,4%). Thus, the usage of Lucas3 chest compression system resulted in 47% while Auto Pulse was 33,3%. The average ambulance arrival time could have had a significant impact on the subsequent effectiveness of cardiopulmonary resuscitation in these cases. Ambulances equipped with Lucas3 reached the destination within 8 minutes, and those with Auto Pulse needed 12,1 minutes. Moreover, taking effective basic life support (BLS) by bystanders before the ambulance arrival was much more frequent for ambulances with Lucas3 than Auto Pulse. Therefore, the percentage of BLS among the group of patients who were employed Lucas3 by METs was 26,5%, and 20,8% for Auto Pulse. The total percentage of taking BLS by bystanders before the ambulance arrival resulted in 25% of patients who were later applied a chest compression system by METs. Not only was shockable cardiac rhythm obtained in 47% of these cases, but an early indication of spontaneous circulation was also provided in all these patients. Both Lucas3 and Auto Pulse were evaluated to be significantly useful in improving the effectiveness of cardiopulmonary resuscitation by 97% of Medical Emergency Teams. Therefore, implementation of chest compression systems essentially makes the cardiopulmonary resuscitation even more effective. The ambulance arrival time, taking successful BLS by bystanders before the ambulance arrival and the presence of shockable cardiac rhythm determine an early indication of spontaneous circulation among patients after a sudden cardiac arrest.

Keywords: cardiac arrest, effectiveness, mechanical chest compression systems, resuscitation

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Authors: Yin Hua Zhang

Abstract:

Cardiac metabolism is essential in myocardial contraction. In addition to glucose, fatty acids (FA) are essential in producing energy in the myocardium since FA-dependent beta-oxidation accounts for > 70-90% of cellular ATP under resting conditions. However, metabolism shifts from FAs to glucose utilization during disease progression (e.g. hypertrophy and ischemic myocardium), where glucose oxidation and glycolysis become the predominant sources of cellular ATP. At advanced failing stage, both glycolysis and beta-oxidation are dysregulated, result in insufficient supply of intracellular ATP and weakened myocardial contractility. Undeniably, our understandings of myocyte function in healthy and diseased hearts are based on glucose (10 mM)-dependent metabolism because glucose is the “sole” metabolic substrate in most of the physiological experiments. In view of the importance of FAs in cardiovascular health and diseases, we aimed to elucidate the impacts of FA supplementation on myocyte contractility and evaluate cellular mechanisms those mediate the functions in normal heart and with pathological stress. In particular, we have investigated cardiac excitation-contraction (E-C) coupling in the presence and absence of FAs in normal and hypertensive rat left ventricular (LV) myocytes. Our results reveal that FAs increase mitochondrial activity, intracellular [Ca²+]i, and LV myocyte contraction in healthy LV myocytes, whereas FA-dependent cardiac inotropyis attenuated in hypertension. FA-dependent myofilament Ca²+ desensitization could be fundamental in regulating [Ca²+]i. Collectively, FAs supplementation resets cardiac E-C coupling scheme in healthy and diseased hearts.

Keywords: hypertension, fatty acid, heart, calcium

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Authors: Paras Agarwal

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Background: Initially believed to be rare, metastases to the eye are the most common ocular malignancy. The choroid’s high perfusion rate not only makes it the most susceptible ocular site for tumour seeding, but also promotes its growth. The cancers most frequently responsible for choroidal metastases originate from the breast and lung, although a significant proportion have unidentified primaries at the time of presentation. Case Presentation: This case report describes a 34 year old female presenting to the ophthalmology department with a one month history of painless distorted vision. On fundus examination, she was noted to have bilateral choroidal lesionsand subsequently underwent a comprehensive diagnostic work-up. The patient was diagnosed with metastatic pulmonary adenocarcinoma, despite lacking conventional risk factors. As she was found to have a mutation in EGFR, the patient was commenced on tyrosine-kinase inhibition with afatinib. The choroidal lesions regressed with a significant improvement in visual acuity and a dramatic anatomical reduction of the choroidal masses. Conclusions: Our case demonstrates the importance of considering metastases as a differential diagnosis for choroidal lesions. Appropriate and thorough history-taking, examination and investigations may be required in order to deduce the underlying cause. Our case is unusual in view of the choroidal lesion being the primary manifestation of metastatic lung cancer in a young patient with no known risk factors. Early recognition of choroidal metastases is important as it is often the first sign of tumour dissemination and will prompt earlier treatment with systemic medications such as chemotherapy, immunotherapy, targeted therapy or hormonal therapy. Our case report also demonstrates the efficacy of afatinib for the treatment of choroidal metastases, with morphological and functional improvements observed with regard to the choroidal metastatic tumour.

Keywords: choroidal neoplasm, choroidal naevus, pulmonary adenocarcinoma, metastases, lung cancer

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Authors: D. F. Zeynalov, T. V. Kartseva, O. V. Sorokin

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Currently, approaches to assess cardiointervalography are based on the calculation of data variance intervals RR. However, they do not allow the evaluation of features related to a period of the cardiac cycle, so how electromechanical phenomena during cardiac subphase are characterized by differently directed changes. Therefore, we have proposed a method of subphase analysis of the cardiac cycle, developed in the department of hominal physiology Novosibirsk State Medical University to identify the features of the dispersion subphase of the cardiac cycle. In the present paper we have examined the 5-minute intervals cardiointervalography (CIG) to isolate RR-, QT-, ST-ranges in healthy children and children with acute respiratory diseases (ARD) in comparison. It is known that primary school-aged children suffer at ARD 5-7 times per year. Consequently, it is one of the most relevant problems in pediatrics. It is known that the spectral indices and indices of temporal analysis of heart rate variability are highly sensitive to the degree of intoxication during immunological process. We believe that the use of subphase analysis of heart rate will allow more thoroughly evaluate responsiveness of the child organism during the course of ARD. The study involved 60 primary school-aged children (30 boys and 30 girls). In order to assess heart rhythm regulation, the record CIG was used on the "VNS-Micro" device of Neurosoft Company (Ivanovo) for 5 minutes in the supine position and 5 minutes during active orthostatic test. Subphase analysis of variance QT-interval and ST-segment was performed on the "KardioBOS" software Biokvant Company (Novosibirsk). In assessing the CIG in the supine position and in during orthostasis of children with acute respiratory diseases only RR-intervals are observed typical trend of general biological reactions through pressosensitive compensation mechanisms to lower blood pressure, but compared with healthy children the severity of the changes is different, of sick children are more pronounced indicators of heart rate regulation. But analysis CIG RR-intervals and analysis subphase ST-segment have yielded conflicting trends, which may be explained by the different nature of the intra- and extracardiac influences on regulatory mechanisms that implement the various phases of the cardiac cycle.

Keywords: acute respiratory diseases, cardiointervalography, subphase analysis, cardiac cycle

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Authors: R. P. Hewawasam, A. F. Dulhunty

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The ryanodine receptor (RyR) is an intracellular ion channel that releases Ca2+ from the sarcoplasmic reticulum and is essential for the excitation-contraction coupling and contraction in striated muscle. Human muscle specific glutathione transferase M2-2 (GSTM2-2) is a highly specific inhibitor of cardiac ryanodine receptor (RyR2) activity. Single channel-lipid bilayer studies and Ca2+ release assays performed using the C-terminal half of the GSTM2-2 and its mutants F157A and Y160A confirmed the ability of the C terminal domain of GSTM2-2 to specifically inhibit the cardiac ryanodine receptor activity. Objective of the present study is to determine the effect of C terminal domain of GSTM2-2 (GSTM2-2C) and the mutants, F157A and Y160A on the Ca2+ transients of neonatal ventricular cardiomyocytes. Primary cardiomyocytes were cultured from neonatal rats. They were treated with GSTM2-2C and the two mutants F157A and Y160A at 15µM and incubated for 2 hours. Then the cells were led with Fluo-4AM, fluorescent Ca2+ indicator, and the field stimulated (1 Hz, 3V and 2ms) cells were excited using the 488 nm argon laser. Contractility of the cells were measured and the Ca2+ transients in the stained cells were imaged using Leica SP5 confocal microscope. Peak amplitude of the Ca2+ transient, rise time and decay time from the peak were measured for each transient. In contrast to GSTM2C which significantly reduced the % shortening (42.8%) in the field stimulated cells, F157A and Y160A failed to reduce the % shortening.Analysis revealed that the average amplitude of the Ca2+ transient was significantly reduced (P<0.001) in cells treated with the wild type GSTM2-2C compared to that of untreated cells. Cells treated with the mutants F157A and Y160A didn’t change the Ca2+ transient significantly compared to the control. A significant increase in the rise time (P< 0.001) and a significant reduction in the decay time (P< 0.001) were observed in cardiomyocytes treated with GSTM2-2C compared to the control but not with F157A and Y160A. These results are consistent with the observation that GSTM2-2C reduced the Ca2+ release from the cardiac SR significantly whereas the mutants, F157A and Y160A didn’t show any effect compared to the control. GSTM2-2C has an isoform-specific effect on the cardiac ryanodine receptor activity and also it inhibits RyR2 channel activity only during diastole. Selective inhibition of RyR2 by GSTM2-2C has significant clinical potential in the treatment of cardiac arrhythmias and heart failure. Since GSTM2-2C-terminal construct has no GST enzyme activity, its introduction to the cardiomyocyte would not exert any unwanted side effects that may alter its enzymatic action. The present study further confirms that GSTM2-2C is capable of decreasing the Ca2+ release from the cardiac SR during diastole. These results raise the future possibility of using GSTM2-2C as a template for therapeutics that can depress RyR2 function when the channel is hyperactive in cardiac arrhythmias and heart failure.

Keywords: arrhythmia, cardiac muscle, cardiac ryanodine receptor, GSTM2-2

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Authors: Parnaz Boodagh, Danila Vella, Antonio Damore, Laura Modica De Mohac, Sang-Ho Ye, Garret Coyan, Gaetano Burriesci, William Wagner, Federica Cosentino

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The use of cardiac patches is among the main therapeutic solution for cardiovascular diseases, a leading mortality cause in the world with an increasing trend, responsible of 19 millions deaths in 2020. Several classes of biomaterials serve that purpose, both of synthetic origin and biological derivation, and many bioengineered treatment alternatives were proposed to satisfy two main requirements, providing structural support and promoting tissue remodeling. The objective of this paper is to compare the mechanical properties and the characterization of four cardiac patches: the Adeka, PhotoFix, CorPatch, and CardioCel patches. In vitro and in vivo tests included: biaxial, uniaxial, ball burst, suture retention for mechanical characterization; 2D surface topography, 3D volume and microstructure, and histology assessments for structure characterization; in vitro test to evaluate platelet deposition, calcium deposition, and macrophage polarization; rat right ventricular outflow tract (RVOT) models at 8- and 16-week time points to characterize the patch-host interaction. Lastly, the four patches were used to produce four stented aortic valve prosthesis, subjected to hydrodynamic assessment as well as durability testing to verify compliance with the standard ISO.

Keywords: cardiac patch, cardiovascular disease, cardiac repair, blood contact biomaterial

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Authors: Matthew Cameron, Stephen Yang, Latifa Al Kharusi, Adam Gosselin, Anissa Chirico, Pouya Gholipour Baradari

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Background: Iron supplementation has been evaluated in several randomized controlled trials (RCTs) for the potential to increase baseline hemoglobin and decrease the incidence of red blood cell (RBC) transfusion during cardiac surgery. This study's main objective was to evaluate the evidence for iron administration in cardiac surgery patients for its effect on the incidence of perioperative RBC transfusion. Methods: This systematic review protocol was registered with PROSPERO (CRD42020161927) on Dec. 19th, 2019, and was prepared as per the PRISMA guidelines. MEDLINE, EMBASE, CENTRAL, Web of Science databases, and Google Scholar were searched for RCTs evaluating perioperative iron administration in adult patients undergoing cardiac surgery. Each abstract was independently reviewed by two reviewers using predefined eligibility criteria. The primary outcome was perioperative RBC transfusion, with secondary outcomes of the number of RBC units transfused, change in ferritin level, reticulocyte count, hemoglobin, and adverse events, after iron administration. The risk of bias was assessed with the Cochrane Collaboration Risk of Bias Tool, and the primary and secondary outcomes were analyzed with a random-effects model. Results: Out of 1556 citations reviewed, five studies (n = 554 patients) met the inclusion criteria. The use of iron demonstrated no difference in transfusion incidence (RR 0.86; 95% CI 0.65 to 1.13). There was a low heterogeneity between studies (I²=0%). The trial sequential analysis suggested an optimal information size of 1132 participants, which the accrued information size did not reach. Conclusion: The current literature does not support the routine use of iron supplementation before cardiac surgery; however, insufficient data is available to draw a definite conclusion. A critical knowledge gap has been identified, and more robust RCTs are required on this topic.

Keywords: cardiac surgery, iron, iron supplementation, perioperative medicine, meta-analysis, systematic review, randomized controlled trial

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Authors: Ali Kassem, Sharf Eldeen-Shazly, Alshemaa Lotfy

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Introduction: Contrast-induced nephropathy (CIN) has been the third leading cause of hospital-acquired renal failure. Patients with cardiac diseases are particularly at risk especially with repeated injections of contrast media. CIN is generally defined as an increase in serum creatinine concentration of > 0.5 mg/dL or 25% above baseline within 48 hours after contrast administration. Aim of work: To examine the frequency of CIN for patients undergoing cardiac catheterization at Sohag University Hospital (Upper Egypt) and to identify possible risk factors for CIN in these patients. Material and methods: The study included 104 patients with mean age 56.11 ±10.03, 64(61.5%) are males while 40(38.5%) are females. 44(42.3%) patients are diabetics, 43(41%) patients are hypertensive, 6(5.7%) patients have congestive heart failure, 69(66.3%) patients on statins, 74 (71.2 %) are on ACEIs or ARBs, 19(15.4%) are on metformin, 6 (5.8%) are on NSAIDs, 30(28.8%) are on diuretics. RESULTS: Patients were classified at the end of the study into two groups: Group A: Included 91 patients who did not develop CIN. Group B: Included 13 patients who developed CIN, of which serum creatinine raised > 0.5mg/dl in 6 patients and raised > 25% from the baseline after the procedure in 13 patients. The overall incidence of CIN was 12.5%. CIN increased with older age. There was an increase in the incidence of CIN in diabetic versus non-diabetic patients (20.5% and 6.7%) respectively. (p< 0.03). There was a highly significant increase in the incidence of CIN in patients with CHF versus those without CHF (100% and 71%) respectively, (P<0001). Patients on diuretics showed a significant increase in the incidence of CIN representing 61.5% of all patients who developed CIN. Conclusion: Older patients, diabetic patients, patients with CHF and patients on diuretics have higher risk of developing CIN during coronary catheterization and should receive reno-protective measures before contrast exposure.

Keywords: cardiac diseases, contrast-induced nephropathy, coronary catheterization, CIN

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Authors: Jolene M. Helena, Annie M. Joubert, Peace Mabeta, Magdalena Coetzee, Roy Lakier, Anne E. Mercier

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Targeting the distant tumour and its microenvironment whilst preserving bone density is important in improving the outcomes of patients with bone metastases. 2-Ethyl-3-O-sulphamoyl-estra1,3,5(10)16-tetraene (ESE-16) is an in-silico-designed 2- methoxyestradiol analogue which aimed at enhancing the parent compound’s cytotoxicity and providing a more favourable pharmacokinetic profile. In this study, the potential radiosensitization effects of ESE-16 were investigated in an in vitro bone metastasis model consisting of murine pre-osteoblastic (MC3T3-E1) and pre-osteoclastic (RAW 264.7) bone cells, metastatic prostate (DU 145) and breast (MDA-MB-231) cancer cells, as well as human umbilical vein endothelial cells (HUVECs). Cytotoxicity studies were conducted on all cell lines via spectrophotometric quantification of 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide. The experimental set-up consisted of flow cytometric analysis of cell cycle progression and apoptosis detection (Annexin V-fluorescein isothiocyanate) to determine the lowest ESE-16 and radiation doses to induce apoptosis and significantly reduce cell viability. Subsequent experiments entailed a 24-hour low-dose ESE-16-exposure followed by a single dose of radiation. Termination proceeded 2, 24 or 48 hours thereafter. The effect of the combination treatment was investigated on osteoclasts via tartrate-resistant acid phosphatase (TRAP) activity- and actin ring formation assays. Tumour cell experiments included investigation of mitotic indices via haematoxylin and eosin staining; pro-apoptotic signalling via spectrophotometric quantification of caspase 3; deoxyribonucleic acid (DNA) damage via micronuclei analysis and histone H2A.X phosphorylation (γ-H2A.X); and Western blot analyses of bone morphogenetic protein-7 and matrix metalloproteinase-9. HUVEC experiments included flow cytometric quantification of cell cycle progression and free radical production; fluorescent examination of cytoskeletal morphology; invasion and migration studies on an xCELLigence platform; and Western blot analyses of hypoxia-inducible factor 1-alpha and vascular endothelial growth factor receptor 1 and 2. Tumour cells yielded half-maximal growth inhibitory concentration (GI50) values in the nanomolar range. ESE-16 concentrations of 235 nM (DU 145) and 176 nM (MDA-MB-231) and a radiation dose of 4 Gy were found to be significant in cell cycle and apoptosis experiments. Bone and endothelial cells were exposed to the same doses as DU 145 cells. Cytotoxicity studies on bone cells reported that RAW 264.7 cells were more sensitive to the combination treatment than MC3T3-E1 cells. Mature osteoclasts were more sensitive than pre-osteoclasts with respect to TRAP activity. However, actin ring morphology was retained. The mitotic arrest was evident in tumour and endothelial cells in the mitotic index and cell cycle experiments. Increased caspase 3 activity and superoxide production indicated pro-apoptotic signalling in tumour and endothelial cells. Increased micronuclei numbers and γ-H2A.X foci indicated increased DNA damage in tumour cells. Compromised actin and tubulin morphologies and decreased invasion and migration were observed in endothelial cells. Western blot analyses revealed reduced metastatic and angiogenic signalling. ESE-16-induced radiosensitization inhibits metastatic signalling and tumour cell survival whilst preferentially preserving bone cells. This low-dose combination treatment strategy may promote the quality of life of patients with metastatic bone disease. Future studies will include 3-dimensional in-vitro and murine in-vivo models.

Keywords: angiogenesis, apoptosis, bone metastasis, cancer, cell migration, cytoskeleton, DNA damage, ESE-16, radiosensitization.

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Authors: Thampi Rawther, Sean O’Brien, Kamala Kanta Das

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Background: Intussusception in the adult is rarely from a benign cause and is almost always pathological. Causes include carcinomas, polyps, Meckel's diverticulum, or colonic diverticulum. Common symptoms include abdominal pain, intestinal obstruction, palpable abdominal mass, GI bleeding, and anemia. Sarcomatoid carcinoma is a rare type of small intestinal malignancy exhibiting carcinomatous and sarcomatous features. It primarily affects older patients, mean age 57, and is 1.5 times more prevalent in men. Method: This is an interesting case report of a patient presenting with intussusception secondary to a sarcomatoid tumor of the small bowel. Conclusion: Surgery is the treatment of choice in adults with intussusception due to the high malignancy potential. Furthermore, surgical resection of the affected bowel is the definitive form of therapy as small bowel sarcomatoid tumors are not responsive to chemotherapy and radiotherapy. Early surgical intervention helps reduce mortality as it allows for early staging, treatment, and monitoring of the tumor. The patient was fortunate to have presented with intussusception, facilitating early surgical intervention, and was found to have a low disease stage.

Keywords: general surgery, small bowel tumour, imaging, unique

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