Search results for: high risk cardiac patients

Authors: Mariia A. Parfenenko, Ilya S. Dantsev, Sergei V. Bochenkov, Natalia V. Vinogradova, Olga S. Groznova, Victoria Yu. Voinova

Abstract:

Introduction: Autism is the most common neurodevelopmental disorder. Autism is characterized by difficulties in social interaction and adherence to stereotypic behavioral patterns and frequently co-occurs with epilepsy, intellectual disabilities, connective tissue disorders, and other conditions. CHD8 codes for chromodomain-helicase-DNA-binding protein 8 - a chromatin remodeler that regulates cellular proliferation and neurodevelopment in embryogenesis. CHD8 is one of the genes most frequently involved in autism. Patients and methods: 2 unrelated male patients, P3 and P12, aged 3 and 12 years old, underwent whole genome sequencing, which determined that they both had different likely pathogenic variants, both previously undescribed in literature. Sanger sequencing later determined that P12 inherited the variant from his affected mother. Results: P3 and P12 presented with autism, a developmental delay, ataxia, sleep disorders, overgrowth, and macrocephaly, as well as other clinical features typically present in patients with causative variants in CHD8. The mother of P12 also has autistic traits, as well as ataxia, hypotonia, sleep disorders, and other symptoms. However, P3 and P12 also have different cardiac abnormalities. P3 had signs of a repolarization disorder: a flattened T wave in the III and aVF derivations and a negative T wave in the V1-V2 derivations. He also had structural valve anomalies with associated regurgitation, local contractility impairment of the left ventricular, and diastolic dysfunction of the right ventricle. Meanwhile, P12 had Wolff-Parkinson-White syndrome and underwent radiofrequency ablation at the age of 2 years. At the time of observation, P12 had mild sinus arrhythmia and an incomplete right bundle branch block, as well as arterial hypertension. Discussion: Cardiac abnormalities were not previously reported in patients with causative variants in CHD8. The underlying mechanism for the formation of those abnormalities is currently unknown. However, the two hypotheses are either a disordered interaction with CHD7 – another chromodomain remodeler known to be directly involved in the cardiophenotype of CHARGE syndrome – a rare condition characterized by coloboma, heart defects and growth abnormalities, or the disrupted functioning of CHD8 as an A-Kinase Anchoring Protein, which are known to modulate cardiac function. Conclusion: We observed 2 unrelated autistic males with likely pathogenic variants in CHD8 that presented with typical symptoms of CHD8-related neurodevelopmental disorder, as well as cardiac abnormalities. Cardiac abnormalities have, until now, been considered uncharacteristic for patients with causative variants in CHD8. Further accumulation of data, including experimental evidence of the involvement of CHD8 in heart formation, will elucidate the mechanism underlying the cardiophenotype of those patients. Acknowledgements: Molecular genetic testing of the patients was made possible by the Charity Fund for medical and social genetic aid projects «Life Genome.»

Keywords: autism spectrum disorders, chromodomain-helicase-DNA-binding protein 8, neurodevelopmental disorder, cardio phenotype

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Authors: Aliya Hisam, Zia Ul Haq, Sohail Aziz, Patrick Doherty, Jill Pell

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Objective: To determine the effectiveness of Mobile health augmented Cardiac rehabilitation (MCard) on health-related quality of life (HRQoL) among post-acute coronary syndrome(post-ACS) patients. Methodology: In a randomized controlled trial, post-ACS patients were randomly allocated (1:1) to an intervention group (received MCard; counseling, empowering with self-monitoring devices, short text messages, in addition to standard post-ACS care) or control group (standard post-ACS care). HRQoL was assessed by generic Short Form-12 and MacNew quality of life myocardial infarction (QLMI) tools. Participants were followed for 24 weeks with data collection and analysis at three-time points (baseline, 12 weeks and 24 weeks). Result: At baseline, 160 patients (80 in each group; mean age 52.66+8.46 years; 126 males, 78.75%) were recruited, of which 121(75.62%) continued and were analyzed at 12-weeks and 119(74.37%) at 24-weeks. The mean SF-12 physical component score significantly improved in the MCard group at 12 weeks follow-up (48.93 vs. control 43.87, p<.001) and 24 weeks (53.52 vs. 46.82 p<.001). The mean SF-12 mental component scores also improved significantly in the MCard group at 12 weeks follow-up (44.84 vs. control 41.40, p<.001) and 24 weeks follow-up (48.95 vs 40.12, p<.001). At 12-and 24-week follow-up, all domains of MacNew QLMI (social, emotional, physical and global) were also statistically significant (p<.001) improved in the MCard group, unlike the control group. Conclusion: MCard is feasible and effective at improving all domains of HRQoL. There was an improvement in physical, mental, social, emotional and global domains among the MCard group in comparison to the control group. The addition of MCard programs to post-ACS standard care may improve patient outcomes and reduce the burden on the health care setting.

Keywords: acute coronary syndrome, mobile health augmented cardiac rehabilitation (MCard), cardiovascular diseases, cardiac rehabilitation, health-related quality of life, short form 12, MacNew QLMI

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Authors: Mende Mensa Sorato, Majid Davari, Abbas Kebriaeezadeh, Nizal Sarrafzadegan, Tamiru Shibru, Behzad Fatemi

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Markov model, like cardiovascular disease (CVD) policy model based simulation, is being used for evaluating the cost-effectiveness of hypertension treatment. Stroke, angina, myocardial infarction (MI), cardiac arrest, and all-cause mortality were included in this model. Hypertension is a risk factor for a number of vascular and cardiac complications and CVD outcomes. Objective: This systematic review was conducted to evaluate the comprehensiveness of this model across different regions globally. Methods: We searched articles written in the English language from PubMed/Medline, Ovid/Medline, Embase, Scopus, Web of Science, and Google scholar with a systematic search query. Results: Thirteen cohort studies involving a total of 2,165,770 (1,666,554 hypertensive adult population and 499,226 adults with treatment-resistant hypertension) were included in this scoping review. Hypertension is clearly associated with coronary heart disease (CHD) and stroke mortality, unstable angina, stable angina, MI, heart failure (HF), sudden cardiac death, transient ischemic attack, ischemic stroke, subarachnoid hemorrhage, intracranial hemorrhage, peripheral arterial disease (PAD), and abdominal aortic aneurism (AAA). Association between HF and hypertension is variable across regions. Treatment resistant hypertension is associated with a higher relative risk of developing major cardiovascular events and all-cause mortality when compared with non-resistant hypertension. However, it is not included in the previous CVD policy model. Conclusion: The CVD policy model used can be used in most regions for the evaluation of the cost-effectiveness of hypertension treatment. However, hypertension is highly associated with HF in Latin America, the Caribbean, Eastern Europe, and Sub-Saharan Africa. Therefore, it is important to consider HF in the CVD policy model for evaluating the cost-effectiveness of hypertension treatment in these regions. We do not suggest the inclusion of PAD and AAA in the CVD policy model for evaluating the cost-effectiveness of hypertension treatment due to a lack of sufficient evidence. Researchers should consider the effect of treatment-resistant hypertension either by including it in the basic model or during setting the model assumptions.

Keywords: cardiovascular disease policy model, cost-effectiveness analysis, hypertension, systematic review, twelve major cardiovascular events

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Authors: Kadeejah Alsolami, Zainab Alrefay, Husaam Awad

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Obesity and vitamin D deficiency have both been related to cardiovascular disease. The present work aimed to investigate the possible protective effect of vitamin D on cardiac apoptosis in a rat model of dietary-induced obesity. Methods: 30 male Wistar rats included in this study. They were allocated into 4 groups: Control (n=5), animal were fed standard diet for 3 months: Control + vitamin D (VD) (n=5),animals were fed a standard diet with 400IU VD/kg for 3 months: hypercaloric diets group (n=10), animals were fed a high fat diet for 3 months: hypercaloric diet with VD group (n=10), animals were fed a high fat diet with 400IU VD/kg for 3 months. At the beginning of the experiment, the weight and length were measured to assess body mass index (BMI) and repeated every 45 days. Food intake and body weight were monitored throughout the study period. Then rats were sacrificed and heart tissues collected for Quantitative Real-time polymerase chain reaction (qRT-PCR). qRT-PCR used to detect different genetic markers of apoptosis (anti-apoptotic gene (BCL2), a pro-apoptotic gene(BAX), pro-apoptotic genes (FAS, FAS-L), tumour necrosis factor (TNF), mitogen-activated protein kinases (MAPK). Results: FAS and FAS-L gene expression were significantly upregulated in rats fed with high fat diet. And FAS-L gene expression was significantly upregulated in all groups on comparison with control. Whereas Bax gene expression was significantly downregulated in rats fed with high-fat diet supplied with vitamin D. TNF was significantly upregulated in rats fed with high-fat diet treated with vitamin D. MAPK was significantly upregulated in rats fed with high fat diet group, and in rats fed with high-fat diet supplied with vitamin D. Conclusion: The cardiac apoptotic pathways were more activated in rats fed with high-fat than lean rats. And vitamin D protect the heart from the cardiac mitochondrial-dependent apoptotic pathway.

Keywords: apoptosis, heart, obesity, Vitamin D

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Authors: Aneta Binkowska, Grzegorz Michalak, Slawomir Pilip, Lukasz Bondaruk, Daniel Celinski, Robert Slotwinski

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Post-traumatic mortality rates are still very high and show an increasing tendency. Early identification of patients at high risk of severe complications has a significant impact on treatment outcomes. The aim of the study was to better understand the early pathological inflammatory response to injury and infection and to determine the usefulness of the assessment of TNF-α and sTNFR1 concentrations in the peripheral blood as early indicators of severe post-traumatic complications. The study was carried out in a group of 51 patients after trauma treated in the ED, including 32 patients that met inclusion criteria for immunological analysis. Patients were divided into two groups using the ISS scale (group A with ISS ≥20, group B with ISS <20). Serum levels of TNF-α and sTNFR1 were determined after admission to the ED and after 3, 6, 12 and 24 hours. The highest TNF-α and sTNFR1 concentrations in both groups were recorded at admission and were significantly higher in group A compared to group B (A vs B TNF-α 2.46 pg/ml vs 1.78 pg/ml; sTNFR1 1667.5 pg/ml vs 875.2 p<0.005). The concentration of sTNFR1 in patients with severe complications was significantly higher compared to patients without complications and preceded clinical symptoms of complications ( C+ vs C- 1561.5 pg/ml vs 930.6 pg/ml). Spearman's correlation showed a statistically significant positive correlation between the baseline concentrations of IL-6 (r=0.38, p<0.043) and sTNFR1 (r=0.59, p=0.001) and the ISS scores. The high diagnostic sensitivity calculated from the ROC (receiver operating characteristic) curves was found for the concentrations of both cytokines: TNF α (AUC=0.91, p=0.004) and sTNFR1 (AUC=0.86, p=0.011). Elevated levels of sTNFR1, determined in the peripheral blood shortly after injury, is significantly associated with the occurrence of later complications, which in some patients lead to death. In contrast, high levels of TNF-α shortly after injury are associated with high mortality.

Keywords: cytokine, SIRS, MODS, trauma

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Authors: Choppala Pratheek, Vineet Ahuja

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Background: Crohn's disease (CD) recurrence following surgery is a common challenge, and current detection methods rely on risk factors identified in Western populations. This study aimed to investigate the risk factors and rates of postoperative CD recurrence in a tuberculosis-endemic region like India. Retrospective data was collected from a structured database from a specialty IBD clinic by reviewing case files from January 2005 to December 2021. Inclusion criteria involved CD patients diagnosed based on the ECCO-ESGAR consensus guidelines, who had undergone at least one intestinal resection and had a minimum follow-up period of one year at the IBD clinic. Results: A total of 90 patients were followed up for a median period of 45 months (IQR, 20.75 - 72.00). Out of the 90 patients, 61 received ATT prior to surgery, with a mean delay in diagnosis of 2.5 years, although statistically non-significant (P=0.078). Clinical recurrence occurred in 50% of patients, with the cumulative rate increasing from 13.3% at one year to 40% at three years. Among 63 patients who underwent endoscopy, 65.7% showed evidence of endoscopic recurrence, with the cumulative rate increasing from 31.7% at one year to 55.5% at four years. Smoking was identified as a significant risk factor for early endoscopic recurrence (P=0.001) by Cox regression analysis, but no other risk factors were identified. Initiating post-operative medications prior to clinical recurrence delayed its onset (P=0.004). Subgroup analysis indicated that endoscopic monitoring aided in the early identification of recurrence (P=0.001). The findings contribute to enhancing post-operative CD management strategies in such regions where the disease burden is escalating.

Keywords: crohns, post operative, tuberculosis-endemic, risk factors

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Authors: Shaine Mehta, Neelam Parmar, Patrick White, Mark Ashworth

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Patients with a history of substance have a high prevalence of comorbidities, including asthma and chronic obstructive pulmonary disease (COPD). Mortality rates are higher than that of the general population and the link to respiratory disease is reported. Randomised controlled trials (RCTs) support opioid substitution therapy as an effective means for harm reduction. However, whilst a high proportion of patients receiving opioid substitution therapy are smokers, to the author’s best knowledge there have been no studies of respiratory disease and smoking intensity in these patients. A cross sectional prevalence study was conducted using an anonymised patient-level database in primary care, Lambeth DataNet (LDN). We included patients aged 18 years and over who had records of ever having been prescribed methadone in primary care. Patients under 18 years old or prescribed buprenorphine (because of uncertainty about the prescribing indication) were excluded. Demographic, smoking, alcohol and asthma and COPD coding data were extracted. Differences between methadone and non-methadone users were explored with multivariable analysis. LDN contained data on 321, 395 patients ≥ 18 years; 676 (0.16%) had a record of methadone prescription. Patients prescribed methadone were more likely to be male (70.7% vs. 50.4%), older (48.9yrs vs. 41.5yrs) and less likely to be from an ethnic minority group (South Asian 2.1% vs. 7.8%; Black African 8.9% vs. 21.4%). Almost all those prescribed methadone were smokers or ex-smokers (97.3% vs. 40.9%); more were non-alcohol drinkers (41.3% vs. 24.3%). We found a high prevalence of COPD (12.4% vs 1.4%) and asthma (14.2% vs 4.4%). Smoking intensity data shows a high prevalence of ≥ 20 cigarettes per day (21.5% vs. 13.1%). Risk of COPD, adjusted for age, gender, ethnicity and deprivation, was raised in smokers: odds ratio 14.81 (95%CI 11.26, 19.47), and in the methadone group: OR 7.51 (95%CI: 5.78, 9.77). Furthermore, after adjustment for smoking intensity (number of cigarettes/day), the risk was raised in methadone group: OR 4.77 (95%CI: 3.13, 7.28). High burden of respiratory disease compounded by the high rates of smoking is a public health concern. This supports an integrated approach to health in patients treated for opiate dependence, with access to smoking cessation support. Further work may evaluate the current structure and commissioning of substance misuse services, including smoking cessation. Regression modelling highlights that methadone as a ‘risk factor’ was independently associated with COPD prevalence, even after adjustment for smoking intensity. This merits further exploration, as the association may be related to unexplored aspects of smoking (such as the number of years smoked) or may be related to other related exposures, such as smoking heroin or crack cocaine.

Keywords: methadone, respiratory disease, smoking cessation, substance misuse

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Authors: Marina Nosik, Irina Rymanova, Konstantin Ryzhov, Joan Yarovaya, Alexander Sobkin

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Tuberculosis (TB) associated with HIV is one of the top causes of death worldwide. However, early detection and treatment of TB in HIV-infected individuals significantly reduces the risk of developing severe forms of TB and mortality. The goal of the study was to analyze the peculiarities of TB associated with HIV infection. Over the period of 2015-2016 a retrospective cohort study was conducted among 377 patients with TB/HIV co-infection who attended the Moscow Tuberculosis Clinic. The majority of the patients was male (64,5%). The median age was: men 37,9 (24÷62) and women 35,4 (22÷72) years. The most prevalent age group was 30-39 years both for men and women (73,3% and 54,7%, respectively). The ratio of patients in age group 50-59 and senior was 3,9%. Socioeconomic status of patients was rather low: only 2.3% of patients had a university degree; 76,1% was unemployed (of whom 21,7% were disabled). Most patients had disseminated pulmonary tuberculosis in the phase of infiltration/ decay (41,5%). The infiltrative TB was detected in 18,9% of patients; 20,1% patients had tuberculosis of intrathoracic lymph nodes. The occurrence of MDR-TB was 16,8% and XDR-TB – 17,9%. The number of HIV-positive patients with newly diagnosed TB was n=261(69,2%). The active TB-form (MbT+) among new TB/HIV cases was 44,7 %. The severe clinical forms of TB and a high TB incidence rate among HIV-infected individuals alongside with a large number of cases of newly diagnosed tuberculosis, indicate the need for more intense interaction with TB services for timely diagnosis of TB which will optimize treatment outcomes.

Keywords: HIV, tuberculosis (TB), TB associated with HIV, multidrug-resistant TB (MDR-TB)

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Authors: Zahra Solgi, Hossein Rassi

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Colorectal cancer (CRC) is a multi-step disease, and chronic gastric infection with H. pylori could play a role in one or more of the steps in this pathogenic process. Polymorphisms in several miRNAs are considered to increase the risk for the development of CRC by controlling proliferation, apoptosis and H. pylori pathogenesis. Therefore, the aim of this study was to investigate miRNA146a rs2910164 polymorphism and Helicobacter pylori infection in CRC. A total of 65 patients with CRC were divided into 2 groups: 28 patients < 50 years of age and 37 patients ≥ 50 years of age. DNA was extracted from all samples by a standard method and H. pylori cagA and miRNA146a rs2910164 genotypes were determined by PCR method. The results show that there was no significant difference in the frequency of H. pylori cagA gene between the two groups but there was a significant difference in the distribution of rs2910164 genotypes in patients < 50 years of age with the p-value of 0.05 and odds ratio equal to 2.69. On other hand, patients < 50 years of age with genotype CC of miRNA146a showed a significant difference in CRC risk. Furthermore, there was a significant correlation between rs2910164 CC genotype with Helicobacter pylori infection in patients < 50 years of age. The present study suggests that the CC genotype of miRNA146a in combination with H. pylori infection can be effective as risk factors and molecular markers for early diagnosis and treatment of CRC.

Keywords: colorectal cancer, Helicobacter pylori, miRNA146a, rs2910164 polymorphism

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Authors: Ledi Neçaj

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Objectives: The target of this paper is (1) to explain objectively physical activity model throughout three chronic cardiopulmonary conditions, and (2) to study the connection among physical activity dimensions with disease severity, self-reported physical and emotional functioning, and exercise performance. Material and Methods: This is a cross-sectional study of patients in their domestic environment. Patients with cardiopulmonary diseases were: chronic obstructive pulmonary disease (COPD), (n-63), coronary heart failure (n=60), and patients with implantable cardioverter defibrillator (n=60). Main results measures: Seven ambulatory physical activity dimensions (total steps, percentage time active, percentage time ambulating at low, medium, and hard intensity, maximum cadence for 30 non-stop minutes, and peak performance) have been measured with an accelerometer. Results: Subjects with COPD had the lowest amount of ambulatory physical activity compared with topics with coronary heart failure and cardiac dysrhythmias (all 7 interest dimensions, P<.05); total step counts have been: 5319 as opposed to 7464 as opposed to 9570, respectively. Six-minute walk distance becomes correlated (r=.44-.65, P<.01) with all physical activity dimensions inside the COPD pattern, the most powerful correlations being with total steps and peak performance. In topics with cardiac impairment, maximal oxygen intake had the most effective small to slight correlations with five of the physical activity dimensions (r=.22-.40, P<.05). In contrast, correlations among 6-minute walk test distance and physical activity have been higher (r=.48-.61, P<.01) albeit in a smaller pattern of most effective patients with coronary heart failure. For all three samples, self-reported physical and mental health functioning, age, frame mass index, airflow obstruction, and ejection fraction had both exceptionally small and no significant correlations with physical activity. Conclusions: Findings from this study present a profitable benchmark of physical activity patterns in individuals with cardiopulmonary diseases for comparison with future studies. All seven dimensions of ambulatory physical activity have disfavor between subjects with COPD, heart failure, and cardiac dysrhythmias. Depending on the research or clinical goal, the use of one dimension, such as total steps, may be sufficient. Although physical activity had high correlations with performance on a six-minute walk test relative to other variables, accelerometers-based physical activity monitoring provides unique, important information about real-world behavior in patients with cardiopulmonary not already captured with existing measures.

Keywords: ambulatory physical activity, walking, monitoring, COPD, heart failure, implantable defibrillator, exercise performance

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Authors: Sara Grazhdani, Alma Cili, Arben Ivanaj

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Immune Thrombocytopenic Purpura is an autoimmune disease characterized by the destruction of platelets by immune mediators, their deficient production in the red bone marrow and increased splenic sequestration, leading to the appearance of thrombocytopenia and increased risk of hemorrhage. Treatment is indicated in patients with low platelet counts (<30 x 10 9 /L) who present clinically with hemorrhagic events or are at increased risk for hemorrhage. The goal of the treatment remains (I) prevention of hemorrhagic events and deaths resulting from them, (II) reaching an adequate level of the number of platelets, (III) treatment of patients with as few toxic effects as possible. Corticosteroid therapy remains the first choice in the treatment of patients with Primary Immune Thrombocytopenic Purpura. Rituximab (Mabthera) remains the first choice in the second line in the treatment of patients with Immune Thrombocytopenic Purpura, refractory to the use of cortisones.

Keywords: ITP, rituximab, prednisolone, relapse

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Authors: Eun Hui Bae, Sang Yeob Lim, Bongseong Kim, Tae Ryom Oh, Su Hyun Song, Sang Heon Suh, Hong Sang Choi, Eun Mi Yang, Chang Seong Kim, Seong Kwon Ma, Kyung-Do Han, Soo Wan Kim

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Background: Recent hypertension guidelines have recommended lower blood pressure (BP) targets in high-risk patients. However, there are no specific guidelines based on age or systolic and diastolic blood pressure (SBP and DBP, respectively). We aimed to assess the effects of age-related BP on the development of end-stage renal disease (ESRD) in patients with diabetes. Methods: A total of 2,563,870 patients with DM aged >20 years were selected from the Korean National Health Screening Program from 2009 to 2012 and followed up until the end of 2019. Participants were categorized into age and BP groups, and the hazard ratios (HRs) for ESRD were calculated. Results: During a median follow-up of 7.15 years, the incidence rates of ESRD increased with increasing SBP and DBP. The HR for ESRD was the highest in patients younger than 40 years of age with DBP ≥ 100 mmHg. The effect of SBP and DBP on ESRD development was attenuated with age (interaction p-value was <0.0001 for age and SBP and 0.0022 for age and DBP). The subgroup analysis for sex, anti-hypertension medication, and history of chronic kidney disease (CKD) showed higher HRs for ESRD among males younger than 40 years, not taking anti-hypertension medications and CKD compared to those among females older than 40 years, anti-hypertension medication and non-CKD groups. Conclusions: Higher SBP and DBP increase the risk of developing ESRD in patients with diabetes, and in particular, younger individuals face greater risk. Therefore, intensive BP management is warranted in younger patients to prevent ESRD.

Keywords: hypertension, young adult, end-stage renal disease, diabetes mellitus, chronic kidney disease, blood pressure

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Authors: J. Byimana, I. A. Muhire, J. E. Nzabahimana, A. Nyombayire

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Introduction: A successful cardiopulmonary resuscitation during a sudden cardiac arrest can be delayed by different components including new hospital setting, lack of adequate training, lack of pre-established resuscitation team and ineffective communication and lead to an unexpected outcome which is death. The main objective of the study was to assess the readiness of resuscitation teams during cardiac arrest and the organizational approaches that would best support their functioning in a new hospital facility, and to detect any factor that may have contributed to responses. This study analyses the readiness of Resuscitation Team (RT) during cardiac arrest. —Material and methods: A prospective Analytic design was carried out at a newly established United Nations level 2 hospital facility, on four RTM (resuscitation team member). A semi structured questionnaire was used to collect data. —Results: This study highlights indicate that the response time during cardiac arrest simulation meet both American heart association (AHA) and European resuscitation council guidelines. The study offers useful evidence about the impact of a new facility on RTM performance and provides an exposure of staff to emergency events within the Work setting.

Keywords: cardiac arrest, code blue, simulation, resuscitation team member

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Authors: Mohamed Majrashi, Patricia Connolly, Terry Gourlay

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Cardiopulmonary bypass is known to cause inflammatory response during open heart surgery. It includes the initiation of different cascades such as coagulation, complement system and cytokines. Although the immune system is body’s key defense mechanism against external assault, when overexpressed, it can be injurious to the patient, particularly in a cohort of patients in which there is a heightened and uncontrolled response. The inflammatory response develops in these patients to an exaggerated level resulting in an autoimmune injury and may lead to poor postoperative outcomes (systemic inflammatory response syndrome and multi-organs failure). Previous studies by this group have suggested a correlation between the level of IL6 measured in patient’s blood before surgery and after polymeric activation and the observed inflammatory response during surgery. Based upon these findings, the present work is aimed at using this response to develop a test which can be used prior to the open heart surgery to identify the high-risk patients before their operation. The work will be accomplished via three main clinical phases including some pilot in-vitro studies, device development and clinical investigation. Current findings from studies using animal blood, employing DEHP and DEHP plasticized PVC materials as the activator, support the earlier results in patient samples. Having established this relationship, ongoing work will focus on developing an activated lateral flow strip technology as a screening device for heightened inflammatory propensity.

Keywords: cardiopulmonary bypass, cytokines, inflammatory response, overexpression

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Authors: Souheila Zemmouchi

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Introduction: Diabetes is currently the leading cause of end-stage chronic kidney disease and dialysis, so it adds additional complexity to the management of chronic hemodialysis patients. These patients are extremely fragile because of their multiple cardiovascular and metabolic comorbidities. Clear and complete description of the experience: the management of a diabetic on hemodialysis is particularly difficult due to frequent hypoglycaemia and significant inter and perdialyticglycemic variability that is difficult to predict. The aim of our study is to describe the clinical-biological profile and to assess the cardiovascular risk of diabetics undergoing chronic hemodialysis, and compare them with non-diabetic hemodialysis patients. Methods: This cross-sectional, descriptive, and analytical study was carried out between January 01 and December 31, 2018, involving 309 hemodialysis patients spread over 4 centersThe data were collected prospectively then compiled and analyzed by the SPSS Version 10 software The FRAMINGHAM RISK SCORE has been used to assess cardiovascular risk in all hemodialysis patients Results: The survey involved 309 hemodialysis patients, including 83 diabetics, for a prevalence of 27% The average age 53 ± 10.2 years. The sex ratio is 1.5. 50% of diabetic hemodialysis patients retained residual diuresis against 32% in non-diabetics. In the group of diabetics, we noted more hypertension (70% versus 38% non-diabetics P 0.004), more intradialytichypoglycemia (15% versus 3% non-diabetics P 0.007), initially, vascular exhaustion was found in 4 diabetics versus 2 non-diabetics. 70% of diabetics with anuria had postdialytichyperglycemia. The study found a statistically significant difference between the different levels of cardiovascular risk according to the diabetic status. Conclusion: There are many challenges in the management of diabetics on hemodialysis, both to optimize glycemic control according to an individualized target and to coordinate comprehensive and effective care.

Keywords: hemodialysis, diabetes, chronic renal failure, glycemic control

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Authors: Omar Nouri, Wafa Mnejja, Nejla Fourati, Fatma Dhouib, Wicem Siala, Ilhem Charfeddine, Afef Khanfir, Jamel Daoud

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Background and objective: Induction chemotherapy (IC) followed by concomitant chemo radiotherapy with intensity modulated radiation (IMRT) technique is actually the recommended treatment modality for locally advanced nasopharyngeal carcinomas (NPC). The aim of this study was to evaluate the prognostic factors predicting loco regional relapse with this new treatment protocol. Patients and methods: A retrospective study of 52 patients with NPC treated between June 2016 and July 2019. All patients received IC according to the protocol of the Head and Neck Radiotherapy Oncology Group (Gortec) NPC 2006 (3 TPF courses) followed by concomitant chemo radiotherapy with weekly cisplatin (40 mg / m2). Patients received IMRT with integrated simultaneous boost (SIB) of 33 daily fractions at a dose of 69.96 Gy for high-risk volume, 60 Gy for intermediate risk volume and 54 Gy for low-risk volume. Median age was 49 years (19-69) with a sex ratio of 3.3. Forty five tumors (86.5%) were classified as stages III - IV according to the 2017 UICC TNM classification. Loco regional relapse (LRR) was defined as a local and/or regional progression that occurs at least 6 months after the end of treatment. Survival analysis was performed according to Kaplan-Meier method and Log-rank test was used to compare anatomy clinical and therapeutic factors that may influence loco regional free survival (LRFS). Results: After a median follow up of 42 months, 6 patients (11.5%) experienced LRR. A metastatic relapse was also noted for 3 of these patients (50%). Target volumes coverage was optimal for all patient with LRR. Four relapses (66.6%) were in high-risk target volume and two (33.3%) were borderline. Three years LRFS was 85,9%. Four factors predicted loco regional relapses: histologic type other than undifferentiated (UCNT) (p=0.027), a macroscopic pre chemotherapy tumor volume exceeding 100 cm³ (p=0.005), a reduction in IC doses exceeding 20% (p=0.016) and a total cumulative cisplatin dose less than 380 mg/m² (p=0.0.34). TNM classification and response to IC did not impact loco regional relapses. Conclusion: For nasopharyngeal carcinoma, tumors with initial high volume and/or histologic type other than UCNT, have a higher risk of loco regional relapse. Therefore, they require a more aggressive therapeutic approaches and a suitable monitoring protocol.

Keywords: loco regional relapse, modulation intensity radiotherapy, nasopharyngeal carcinoma, prognostic factors

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Authors: Christopher G. Harris, Guy D. Eslick

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Purpose: Lobular carcinoma in situ (LCIS) is a known risk factor for breast cancer of unclear significance when detected in association with invasive carcinoma. This meta-analysis aims to determine the impact of LCIS on local recurrence risk for individuals with breast cancer treated with breast conservation therapy to help guide appropriate treatment strategies. Methods: We identified relevant studies from five electronic databases. Studies were deemed suitable for inclusion where they compared patients with invasive breast cancer and concurrent LCIS to those with breast cancer alone, all patients underwent breast conservation therapy (lumpectomy with adjuvant radiation therapy), and local recurrence was evaluated. Recurrence data were pooled by use of a random effects model. Results: From 1488 citations screened by our search, 8 studies were deemed suitable for inclusion. These studies comprised of 908 cases and 10638 controls. Median follow-up time was 90 months. There was a significantly increased overall risk of local breast cancer recurrence for individuals with LCIS in association with breast cancer following breast conservation therapy [pOR 1.87; 95% CI 1.14-3.04; p = 0.012]. The risk of local recurrence was non-significantly increased at 5 [pOR 1.09; 95% CI 0.48-2.48; p = 0.828] and 10 years [pOR 1.90; 95% CI 0.89-4.06; p = 0.096]. Conclusions: Individuals with LCIS in association with invasive breast cancer have an increased risk of local recurrence following breast conservation therapy. This supports consideration of aggressive local control of LCIS by way of completion mastectomy or re-excision for certain high-risk patients.

Keywords: breast cancer, breast conservation therapy, lobular carcinoma in situ, lobular neoplasia, local recurrence, meta-analysis

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Authors: Leonardo Juan Ramírez López, Javier Oswaldo Rodriguez Velasquez

Abstract:

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: Yori Gidron, Maartje Mol, Norbert Foudraine, Frits Van Osch, Joop Van Den Bergh, Moshe Farchi, Maud Straus

Abstract:

Background: The worldwide pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-COV2), which began in 2019, also known as Covid-19, has infected over 136 million people and tragically took the lives of over 2.9 million people worldwide. Many of the complications and deaths are predicted by the inflammatory “cytokine storm.” One way to progress in the prevention of death is by finding a predictive and protective factor that inhibits inflammation, on the one hand, and which also increases anti-viral immunity on the other hand. The vagal nerve does precisely both actions. This study examined whether vagal nerve activity, indexed by heart-rate variability (HRV), predicts survival in patients with Covid-19. Method: We performed a pseudo-prospective study, where we retroactively obtained ECGs of 271 Covid-19 patients arriving at a large regional hospital in The Netherlands. HRV was indexed by the standard deviation of the intervals between normal heartbeats (SDNN). We examined patients’ survival at 3 weeks and took into account multiple confounders and known prognostic factors (e.g., age, heart disease, diabetes, hypertension). Results: Patients’ mean age was 68 (range: 25-95) and nearly 22% of the patients had died by 3 weeks. Their mean SDNN (17.47msec) was far below the norm (50msec). Importantly, relatively higher HRV significantly predicted a higher chance of survival, after statistically controlling for patients’ age, cardiac diseases, hypertension and diabetes (relative risk, H.R, and 95% confidence interval (95%CI): H.R = 0.49, 95%CI: 0.26 – 0.95, p < 0.05). However, since HRV declines rapidly with age and since age is a profound predictor in Covid-19, we split the sample by median age (40). Subsequently, we found that higher HRV significantly predicted greater survival in patients older than 70 (H.R = 0.35, 95%CI: 0.16 – 0.78, p = 0.01), but HRV did not predict survival in patients below age 70 years (H.R = 1.11, 95%CI: 0.37 – 3.28, p > 0.05). Conclusions: To the best of our knowledge, this is the first study showing that higher vagal nerve activity, as indexed by HRV, is an independent predictor of higher chances for survival in Covid-19. The results are in line with the protective role of the vagal nerve in diseases and extend this to a severe infectious illness. Studies should replicate these findings and then test in controlled trials whether activating the vagus nerve may prevent mortality in Covid-19.

Keywords: Covid-19, heart-rate Variability, prognosis, survival, vagal nerve

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Authors: Jeena R. S., Sukesh Kumar A.

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Stroke is one of the major reasons of adult disability and morbidity in many of the developing countries like India. Early diagnosis of stroke is essential for timely prevention and cure. Various conventional statistical methods and computational intelligent models have been developed for predicting the risk and outcome of stroke. This research work focuses on a multilevel approach for predicting the occurrence of stroke based on various risk factors and invasive techniques like retinal imaging. This risk prediction model can aid in clinical decision making and help patients to have an improved and reliable risk prediction.

Keywords: prediction, retinal imaging, risk factors, stroke

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Authors: Inkyong Yi

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Acute kidney injury (AKI) in trauma patients is known to be associated with multiple factors, especially shock and consequent inadequate renal perfusion, yet its clinical presentation is little known in severe trauma patients. Our aim was to investigate the clinical presentation of acute kidney injury and its outcome in severe trauma patients at a level I trauma center. A total of 93 consecutive adult trauma patients with an injury severity score (ISS) of more than 15 were analyzed retrospectively from our Level I trauma center data base. Patients with direct renal injury were excluded. Patients were dichotomized into two groups, according to the presence of AKI. Various clinical parameters were compared between two groups, with Student’s T test and Mann-Whitney’s U test. The AKI group was further dichotomized into patients who recovered within seven days, and those who required more than 7days for recovery or those who did not recover at all. Various clinical parameters associated with outcome were further analyzed. Patients with AKI (n=33, 35%) presented with significantly higher age (61.4±17.3 vs. 45.4±17.3, p < 0.0001), incidence of comorbidities (hypertension; 51.5% vs. 13.3%, OR 6.906 95%CI 2.515-18.967, diabetes; 27.3% vs. 6.7%, OR 5.250, 95%CI 1.472-18.722), odds of head and neck trauma (69.7% vs. 41.7%, OR 3.220, 95%CI 1.306-7.942) and presence of shock during emergency room care (66.7% vs 21.7% OR 7.231, 95%CI, 2.798-18.687). Among AKI patients, patients who recovered within 1 week showed lower peak lactate (4.7mmol/L, 95%CI 2.9-6.5 vs 7.3mmol/L, 95%CI 5.0-9.6, p < 0.0287), lesser units of transfusion during first 24 hours (pRBC; 20.4unit, 95%CI 12.5-28.3 vs. 58.9unit, 95%CI 39.4-78.5, p=0.0003, FFP; 16.6unit, 95%CI 6.8-26.4 vs. 56.1unit, 95%CI 26.9-85.2, p=0.0027). In severe trauma patients, patients with AKI showed different clinical presentations and worse outcomes. Initial presence of shock and higher DIC profiles may be important risk factors for AKI in severe trauma patients. In patients with AKI, peak lactate level and amounts of transfusion are related to recovery.

Keywords: acute kidney injury, lactate, transfusion, trauma

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Authors: Mai Ashraf Talaat

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Objectives: The aim of this review article is to assess the success of dental implants in breast cancer patients receiving bisphosphonate therapy and to evaluate the risk of developing bisphosphonate-related osteonecrosis of the jaw following dental implant surgery. Materials and Methods: A thorough search was conducted, with no time or language restriction, using: PubMed, PubMed Central, Web of Science, and ResearchGate electronic databases. Medical Subject Headings (MeSH) terms such as “bisphosphonate”, “dental implant”, “bisphosphonate-related osteonecrosis of the jaw (BRONJ)”, “osteonecrosis”, “breast cancer, MRONJ”, and their related entry terms were used. Eligibility criteria included studies and clinical trials that evaluated the impact of bisphosphonates on dental implants. Conclusion: Breast cancer patients undergoing bisphosphonate therapy may receive dental implants. However, the risk of developing BRONJ and implant failure is high. Risk factors such as the type of BP received, the route of administration, and the length of treatment prior to surgery should be considered. More randomized controlled trials with long-term follow-ups are needed to draw more evidence-based conclusions.

Keywords: dental implants, breast cancer, bisphosphonates, osteonecrosis, bisphosphonate-related osteonecrosis of the jaw

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Authors: Canga Mimoza, Irene Malagnino, Giulia Malagnino, Vito Malagnino

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Aim: This study aims at evaluating the impact of total dust (LGS) and mineral dust (PM10), in the cardio vascular and respiratory systems. Also proving that these air polluters are the cause of several diseases, such as bronchopneumonia, pneumonia, bronchitis, angina pectoris and cardiac insufficiency. Material and Method: The study is concentrated in the cities of Fier and Vlora. This is a clinic-epidemiological study conducted during the time period 2014-2019. Some of the data of LGS and PM10 were obtained from the database of the Institute of Public Health. The formula to measure the mean value of LGS and PM10 is ∆X=X (mean)-Xᵢ. Results: Based on the calculations made, we noticed that: The mean value of LGS in the city of Fieri was 227,33, while the mean value of LGS in the city of Vlora was 177,4. Whereas, the mean value of PM10 in the city of Fieri was 105.5 and the mean value of PM10 in the city of Vlore was 77.5. According to, our statistics the values of LGS were 1.2 times higher in Fier than in Vlora and the PM10 values were 1.36 times higher in Fier than in Vlora. Based on the data, in the city of Fier, the incidence of the bronchopneumonia was 56.53 sick patients/1000 inhabitants, but in Vlora, it was 22 sick patients/1000 inhabitants, so the number of the sick patients was 2.5 times higher in the city of Fieri compared with Vlora city, (P=0.001). The number of the patients with bronchitis, in the city of Fier, was 18 patients/1000 inhabitants, whereas, in Vlora, it was 9 patients/1000 inhabitants, (P=0.005). Based on the data, 8 patients/1000 inhabitants in the city of Fier, suffered from the pneumonia disease, while in Vlora city, were 4 patients/1000 inhabitants, (P=0.005). Another disease taken in consideration was angina pectoris. This study can claim that in the city of Fier, 9.5 patients/1000 inhabitants suffered from this disease, while in Vlora city, were only 4 patients /1000 inhabitants, (P=0.001). Findings of the present study proved that 3.7 patients/1000 inhabitants in the city of Fieri, had cardiac insufficiency, whereas in the city of Vlora, were 1.8 patients/1000 inhabitants, (P=0.05). Conclusions: LGS and PM10 have an influential impact on the cardio vascular and respiratory system; that’s why their levels should be kept under control. The pollution levels are 1.2 and 1.4 times higher in Fier than in Vlora; also the incidences of the diseases are 2 times higher in Fier than in Vlora. Recommendations: In order to prevent the cardio vascular and respiratory diseases, we should avoid places where pollution is higher than the norm. This can be achieved by frequenting places where the air pollution is lower, such as parks, gardens, top floors, etc.

Keywords: impact of total dust, LGS, mineral dust, PM 10, cardio vascular pathologies, respiratory disease

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Authors: Yiyuan David Hu, Alex Lindqwister, Samuel B. Klein, Karen Moodie, Norman A. Paradis

Abstract:

Introduction: Pseudo-Pulseless Electrical Activity (p-PEA) is a lifeless form of profound cardiac shock characterized by measurable cardiac mechanical activity without clinically detectable pulses. Patients in pseudo-PEA carry different prognoses than those in true PEA and may require different therapies. End-tidal carbon dioxide (ET-CO2) has been studied in ventricular fibrillation and true PEA but in p-PEA. We utilized an hypoxic porcine model to characterize the performance of ET-CO2 in resuscitation from p-PEA. Hypothesis: Capnography correlates to the number of required interventions for resuscitation from p-PEA. Methods: Female swine (N = 14) under intravenous anesthesia were instrumented with aortic and right atrial micromanometer pressure. ECG and ET-CO2 were measured continuously. p-PEA was induced by ventilation with 6% oxygen in 94% nitrogen and was defined as a systolic aortic (Ao) pressure less than 40 mmHg. Pigs were grouped based on the interventions required to achieve ROSC: 100%O2, 100%O2 + CPR, 100%O2 + CPR + epinephrine. Results: End tidal CO2 reliably predicted O2 therapy vs CPR-based interventions needed for resuscitation (Figure 1). Pigs who would recover with 100%O2 only had a mean ET-CO2 slope of 0.039 ± 0.013 [ R2 = 0.68], those requiring oxygen + CPR had a slope of -0.15 ± 0.016 [R2 = 0.95], and those requiring oxygen + CPR + epinephrine had a slope of -0.12 ± 0.031 [R2 = 0.79]. Conclusions: In a porcine model of hypoxic p-PEA, measured ET-CO2 appears to be strongly correlated with the required interventions needed for ROSC. If confirmed clinically, these results indicate that ET-CO2 may be useful in guiding therapy in patients suffering p-PEA cardiac arrest.

Keywords: pseudo-PEA, resuscitation, capnography, hypoxic pseudo-PEA

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Authors: Suvorov Vasyl, Filipchuk Viktor

Abstract:

Background: If non-surgical treatment of developmental dysplasia of the hip (DDH) fails or if DDH is late-detected, surgery is necessary. Salter pelvic osteotomy (SPO) is an effective surgical option for such cases. The objectives of this study were to assess the results after SPO, evaluate risk factors, and reveal those radiological parameters that may correlate with the results. Mid- and long-term postoperative results after SPO in 17 patients (22 hip joints) were analyzed. Risk factors included those that do not depend on the surgeon (patient's age, value of the acetabular index (AI) preoperatively, DDH Tonnis grade) and those that depend on the surgeon (amount of AI correction). To radiological parameters which may correlate with the amount of AI correction, we referred distance "d" and the lateral rotation angle. Results: SPO allows performing AI correction in ranges 24.1 ± 6.5°. Excellent and good clinical results were obtained in 95.5% of patients; excellent and good radiological results in 86.4% of patients. Risk factors that do not depend on the surgeon were older patient’s age and higher preoperative AI values (p < 0.05). The risk factor that depends on the surgeon was the amount of AI correction (p < 0.05). The distance "d" was recognized as a radiological parameter that may indicate sufficient AI correction (p < 0.05). Conclusion: In older patients with a higher preoperative AI value, the results will be predictably worse. The surgeon may influence the result with a greater amount of AI correction (which may also be indicated radiologically by the distance "d" values).

Keywords: developmental dysplasia of the hip, results, risk factor, pelvic osteotomy, salter osteotomy

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Authors: Ali Kassem, Esam Nada, Amro Abdelhamed, Shigeo Horie

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Objective: Diabetes mellitus (DM) is associated with macrovascular complications, including coronary artery disease (CAD), and microvascular complications that contribute to the pathogenesis of erectile dysfunction (ED). On the other hand, silent myocardial ischemia (SMI) is more common in diabetic patients and is a strong predictor of cardiac events and mortality in diabetic and non-diabetic patients. Recently, Multidetector computed tomographic coronary angiography (MDCT-CA) has become a reliable non-invasive imaging modality for screening diabetic patients for SMI. We aim to evaluate the presence of SMI using (MDCT-CA) in patients with type 2DM having ED. Methods: This study evaluated 20 patients (mean age 61.45 ± 10.7 years), with DM and ED without any history of angina or angina equivalent. ED was tested with the Sexual Health Inventory for Men score, erection hardness score (EHS), and maximal penile circumferential change by an erect meter. Results: Of twenty studied patients, coronary artery stenosis was detected in 13 (65%) patients in the form of one-vessel disease (n = 6, 30%), two-vessel disease (n = 2, 10%), and three-vessel disease (n = 5, 25%). Maximum coronary artery stenosis was positively correlated with age (P < 0.016,) and negatively correlated with EHS (P <04). Multivariate regression analysis using age and EHS showed that age was the only independent predictor of SMI (P <04). Conclusion: MDCT-CA is a useful tool to identify SMI in patients with diabetes mellitus and ED. One should consider the possibility of SMI especially in elderly patients with DM who have ED.

Keywords: diabetes mellitus, erectile dysfunction, microvascular, silent ischemia

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Authors: F. Kovács, K. Kádár, G. Hosszú, Á. T. Balogh, T. Zsedrovits, N. Kersner, A. Nagy, Gy. Jeney

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The paper presents a novel screening method to indicate congenital heart diseases (CHD), which otherwise could remain undetected because of their low level. Therefore, not belonging to the high-risk population, the pregnancies are not subject to the regular fetal monitoring with ultrasound echocardiography. Based on the fact that CHD is a morphological defect of the heart causing turbulent blood flow, the turbulence appears as a murmur, which can be detected by fetal phonocardiography (fPCG). The proposed method applies measurements on the maternal abdomen and from the recorded sound signal a sophisticated processing determines the fetal heart murmur. The paper describes the problems and the additional advantages of the fPCG method including the possibility of measurements at home and its combination with the prescribed regular cardiotocographic (CTG) monitoring. The proposed screening process implemented on a telemedicine system provides an enhanced safety against hidden cardiac diseases.

Keywords: cardiac murmurs, fetal phonocardiography, screening of CHDs, telemedicine system

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Authors: Mohammadjavad Sotoudeheian, Navid Farahmandian

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Cardiac hypertrophy arises in response to persistent increases in hemodynamic loads. In comparison, diabetic cardiomyopathy is defined by an abnormal myocardial changes without other cardiac-related risk factors. Pathological cardiac hypertrophy and myocardial remodeling are hallmarks of cardiovascular diseases and are risk factors for heart failure. The transcription factor forkhead box class O (FOXOs) can protect heart tissue by hostile oxidative stress and stimulating apoptosis and autophagy. FOXO proteins, as sensitive elements and mediators in response to environmental changes, have been revealed to prevent and inverse cardiac hypertrophy. FOXOs are inhibited by insulin and are critical mediators of insulin action. Insulin deficiency and uncontrolled diabetes lead to a catabolic state. FOXO1 acts downstream of the insulin-dependent pathways, which are dysregulated in diabetes. It regulates cardiomyocyte hypertrophy downstream of IGF1R/PI3K/Akt activation, which are critical regulators of cardiac hypertrophy. The complex network of signaling pathways comprising insulin/IGF-1 signaling, AMPK, JNK, and Sirtuins regulate the development of cardiovascular dysfunction by modulating the activity of FOXOs. Insulin receptors and IGF1R act via the PI3k/Akt and the MAPK/ERK pathways. Activation of Akt in response to insulin or IGF-1 induces phosphorylation of FOXOs. Increased protein synthesis induced by activation of the IGF-I/Akt/mTOR signaling pathway leads to hypertrophy. This pathway and the myostatin/Smad pathway are potent negative muscle development regulators. In cardiac muscle, insulin receptor substrates (IRS)-1 or IRS-2 activates the Akt signaling pathway and inactivate FOXO1. Under metabolic stress, p38 MAPK promotes degradation of IRS-1 and IRS-2 in cardiac myocytes and activates FOXO1, leading to cardiomyopathy. Sirt1 and FOXO1 interaction play an essential role in starvation-induced autophagy in cardiac metabolism. Inhibition of Angiotensin-II induced cardiomyocyte hypertrophy is associated with reduced FOXO1 acetylation and activation of Sirt1. The NF-κB, ERK, and FOXOs are de-acetylated by SIRT1. De-acetylation of FOXO1 induces the expression of genes involved in autophagy and stimulates autophagy flux. Therefore, under metabolic stress, FOXO1 can cause diabetic cardiomyopathy. The overexpression of FOXO1 leads to decreased cardiomyocyte size and suppresses cardiac hypertrophy through inhibition of the calcineurin–NFAT pathway. Diabetes mellitus is associated with elevation of O-GlcNAcylation. Some of its binding partners regulate the substrate selectivity of O-GlcNAc transferase (OGT). O-GlcNAcylation of essential contractile proteins may inhibit protein-protein interactions, reduce calcium sensitivity, and modulate contractile function. Uridine diphosphate (UDP)-GlcNAc is the obligatory substrate of OGT, which catalyzes a reversible post-translational protein modification. The increase of O-GlcNAcylation is accompanied by impaired cardiac hypertrophy in diabetic hearts. Inhibition of O-GlcNAcylation blocks activation of ERK1/2 and hypertrophic growth. O-GlcNAc modification on NFAT is required for its translocation from the cytosol to the nucleus, where NFAT stimulates the transcription of various hypertrophic genes. Inhibition of O-GlcNAcylation dampens NFAT-induced cardiac hypertrophic growth. Transcriptional activity of FOXO1 is enriched by improved O-GlcNAcylation upon high glucose stimulation or OGT overexpression. In diabetic conditions, the modification of FOXO1 by O-GlcNAc is promoted in cardiac troponin I and myosin light chain 2. Therefore targeting O-GlcNAcylation represents a potential therapeutic option to prevent hypertrophy in the diabetic heart.

Keywords: diabetes, cardiac hypertrophy, O-GlcNAcylation, FOXO1, Akt, PI3K, AMPK, insulin

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Authors: Abhaydeep Pandey, Shweta Shukla, Saptamita Goswami, Bhaswati Bandyopadhyay, Vishnampettai Ramachandran, Sudhanshu Vrati, Arup Banerjee

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Dengue virus infection is now considered as one of the most important mosquito-borne infection in human. The virus is known to promote vascular permeability, cerebral edema leading to Dengue hemorrhagic fever (DHF) or Dengue shock syndrome (DSS). Dengue infection has known to be endemic in India for over two centuries as a benign and self-limited disease. In the last couple of years, the disease symptoms have changed, manifesting severe secondary complication. So far, Delhi has experienced 12 outbreaks of dengue virus infection since 1997 with the last reported in 2014-15. Without specific antivirals, the case management of high-risk dengue patients entirely relies on supportive care, involving constant monitoring and timely fluid support to prevent hypovolemic shock. Nonetheless, the diverse clinical spectrum of dengue disease, as well as its initial similarity to other viral febrile illnesses, presents a challenge in the early identification of this high-risk group. WHO recommends the use of warning signs to identify high-risk patients, but warning signs generally appear during, or just one day before the development of severe illness, thus, providing only a narrow window for clinical intervention. The ability to predict which patient may develop DHF and DSS may improve the triage and treatment. With the recent discovery of high throughput RNA sequencing allows us to understand the disease progression at the genomic level. Here, we will collate the results of RNA-Sequencing data obtained recently from PBMC of different categories of dengue patients from India and will discuss the possible role of deregulated genes and long non-coding RNAs NEAT1 for development of disease progression.

Keywords: long non-coding RNA (lncRNA), dengue, peripheral blood mononuclear cell (PBMC), nuclear enriched abundant transcript 1 (NEAT1), dengue hemorrhagic fever (DHF), dengue shock syndrome (DSS)

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Authors: Hernán A. Perez, Luis J. Armando, Néstor H. García

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Background and aims Cardiovascular disease rates are very high in patients with renal failure (CRF), but the underlying mechanisms are incompletely understood. Traditional cardiovascular risk factors do not explain the increased risk, and observational studies have observed paradoxical or absent associations between classical risk factors and mortality in dialysis patients. A large randomized controlled trial, the 4D Study, the AURORA and the ALERT study found that statin therapy in CRF do not reduce cardiovascular events. These results may be the results of ‘accelerated atherosclerosis’ observed on these patients. The objective of this study was to investigate if carotid total plaque area (TPA), a measure of carotid plaque burden growth is increased at progressively lower creatinine clearance in patients with CRF. We studied a cohort of patients with CRF not on dialysis, reasoning that risk factor associations might be more easily discerned before end stage renal disease. Methods: The Blossom DMO Argentina ethics committee approved the study and informed consent from each participant was obtained. We performed a cohort study in 412 patients with Stage 1, 2 and 3 CRF. Clinical and laboratory data were obtained. TPA was determined using bilateral carotid ultrasonography. Modification of Diet in Renal Disease estimation formula was used to determine renal function. ANOVA was used when appropriate. Results: Stage 1 CRF group (n= 16, 43±2yo) had a blood pressure of 123±2/78±2 mmHg, BMI 30±1, LDL col 145±10 mg/dl, HbA1c 5.8±0.4% and had the lowest TPA 25.8±6.9 mm2. Stage 2 CRF (n=231, 50±1 yo) had a blood pressure of 132±1/81±1 mmHg, LDL col 125±2 mg/dl, HbA1c 6±0.1% and TPA 48±10mm2 ( p< 0.05 vs CRF stage 1) while Stage 3 CRF (n=165, 59±1 yo) had a blood pressure of 134±1/81±1, LDL col 125±3 mg/dl, HbA1c 6±0.1% and TPA 71±6mm2 (p < 0.05 vs CRF stage 1 and 2). Conclusion: Our data indicate that TPA increases along the renal function deterioration, and it is not related with the LDL cholesterol and triglycerides levels. We suggest that mechanisms other than the classics are responsible for the observed excess of cardiovascular disease in CKD patients and finally, determination of total plaque area should be used to measure effects of antiatherosclerotic therapy.

Keywords: hypertension, chronic renal failure, atherosclerosis, cholesterol

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