scholarly journals Age-Associated TET2 Mutations: Common Drivers of Myeloid Dysfunction, Cancer and Cardiovascular Disease

2020 ◽  
Vol 21 (2) ◽  
pp. 626 ◽  
Author(s):  
Christina K. Ferrone ◽  
Mackenzie Blydt-Hansen ◽  
Michael J. Rauh
Keyword(s):  
Cardiovascular Disease ◽  
Inflammatory Diseases ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Hematopoietic Stem ◽  
Increased Risk ◽  
On Chip ◽  
Developed World ◽  
The Impact ◽  
Inactivating Mutations

Acquired, inactivating mutations in Tet methylcytosine dioxygenase 2 (TET2) are detected in peripheral blood cells of a remarkable 5%–10% of adults greater than 65 years of age. They impart a hematopoietic stem cell advantage and resultant clonal hematopoiesis of indeterminate potential (CHIP) with skewed myelomonocytic differentiation. CHIP is associated with an overall increased risk of transformation to a hematological malignancy, especially myeloproliferative and myelodysplastic neoplasms (MPN, MDS) and acute myeloid leukemia (AML), of approximately 0.5% to 1% per year. However, it is becoming increasingly possible to identify individuals at greatest risk, based on CHIP mutational characteristics. CHIP, and particularly TET2-mutant CHIP, is also a novel, significant risk factor for cardiovascular diseases, related in part to hyper-inflammatory, progeny macrophages carrying TET2 mutations. Therefore, somatic TET2 mutations contribute to myeloid expansion and innate immune dysregulation with age and contribute to prevalent diseases in the developed world—cancer and cardiovascular disease. Herein, we describe the impact of detecting TET2 mutations in the clinical setting. We also present the rationale and promise for targeting TET2-mutant and other CHIP clones, and their inflammatory environment, as potential means of lessening risk of myeloid cancer development and dampening CHIP-comorbid inflammatory diseases.

scholarly journals Television Viewing and Cognitive Dysfunction of Korean Older Adults

Healthcare ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 547
Author(s):  
Mi Sook Jung ◽  
Eunyoung Chung
Keyword(s):  
Older Adults ◽  
Cognitive Dysfunction ◽  
Cognitive Aging ◽  
Significant Risk ◽  
Multivariate Logistic Regression Analysis ◽  
Later Life ◽  
Significant Risk Factor ◽  
Tv Viewing ◽  
Increased Risk ◽  
The Impact

This study examined the association between television (TV) viewing and cognitive dysfunction in elderly Koreans. Among participants of the 2014 National Survey of Older Koreans, 9644 were considered in this study. To better identify the association between two factors, propensity score (PS) matching with exact method was used. Finally, 168 viewers and non-viewers each were selected based on estimated PS on key variables and eliminating double matches. Multivariate logistic regression analysis was performed when controlling for possible covariates. Viewers were more likely to have cognitive dysfunction than non-viewers, with significant differences in most covariates. After correcting confounding effects of these covariates with PS matching, TV viewing was found to be a significant risk factor of cognitive dysfunction, along with absence of diagnosed hypertension and non-participation in physical leisure activities. TV viewing might be associated with increased risk of cognitive dysfunction in later life. Appropriate education and strategies to minimize TV viewing among older adults should be established to contribute to attenuating cognitive aging. More interventional studies can help older adults, caregivers, and healthcare professionals explore the cognitively beneficial alternatives to TV use considering the impact of socioeconomic factors of selecting TV viewing as a preferred leisure activity.

Tolerability of Highly Protein Bound Targeted Oral Oncolytic Drugs in Patients With Hypoalbuminemia: A Retrospective Analysis

2020 ◽  
Vol 55 (2) ◽  
pp. 165-173
Author(s):  
Joshua L. Murdock ◽  
Marissa R. Duco ◽  
David J. Reeves
Keyword(s):  
Cox Regression ◽  
Serum Proteins ◽  
Significant Risk ◽  
Dose Intensity ◽  
Significant Risk Factor ◽  
Oncolytic Therapy ◽  
Drug Tolerability ◽  
Increased Risk ◽  
The Impact ◽  
Similar Incidence

Background: Hypoalbuminemia is commonly observed in cancer patients. Given the pharmacokinetic interactions between serum proteins and protein bound medications, administration of highly protein bound targeted oral oncolytic drugs may result in elevated unbound drug levels and decreased tolerability in those with hypoalbuminemia. Objective: To describe the impact of hypoalbuminemia on oral oncolytic drug tolerability. Methods: A retrospective study was conducted of adult patients receiving treatment with targeted oral oncolytic drugs with ≥95% protein binding. The primary end point of this study was to compare time to discontinuation resulting from documented toxicity in those with and without hypoalbuminemia. Results: The study included 143 patients receiving 16 targeted oral oncolytic drugs (42% with hypoalbuminemia, 58% without hypoalbuminemia). Adverse events were common, with similar incidence among patients with and without hypoalbuminemia (73% vs 76%, respectively; P = 0.727). Median time to therapy discontinuation resulting from documented toxicity was significantly shorter in those with hypoalbuminemia (22 months vs not reached; P = 0.003). Cox regression demonstrated that hypoalbuminemia was the only significant risk factor for shorter time to discontinuation resulting from documented adverse effects (hazard ratio = 3.0; 95% CI = 1.15-8.0; P = 0.025). Conclusion and Relevance: This represents the first report of the impact of hypoalbuminemia on tolerability of highly protein bound oral oncolytic drugs, demonstrating that patients with hypoalbuminemia may be at increased risk for early discontinuation resulting from toxicity. Given the importance of maintaining dose intensity in patients receiving oncolytic therapy, albumin levels should be monitored throughout treatment and supportive care maximized in those developing hypoalbuminemia.

The Impact of Partner Stalking on Mental Health and Protective Order Outcomes Over Time

2007 ◽  
Vol 22 (5) ◽  
pp. 546-562 ◽  
Author(s):  
TK Logan ◽  
Jennifer Cole
Keyword(s):  
Mental Health ◽  
Partner Violence ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Protective Order ◽  
Increased Risk ◽  
Women’S Perceptions ◽  
Psychological Harm ◽  
The Impact ◽  
Over Time

The goals of this article are to examine stalking victimization over time among a large sample (n = 662) of women who received a protective order against a violent partner and to examine the impact of stalking on mental health and protective order outcomes. Findings suggest that stalking is a significant risk factor for other forms of partner violence (e.g., psychological, physical, and sexual violence) and that the experience of being stalked by a violent partner contributes uniquely to women’s perceptions of psychological distress, personal safety, and perceptions of protective order effectiveness. Both the criminal justice system and victim service representatives need to be vigilant in educating women about the increased risk of stalking to their safety and mental health. Further, study findings suggest that stalking must be addressed to prevent future physical and psychological harm in partner violence cases.

scholarly journals Fluoxetine treatment prevents cardiovascular changes in baroreflex and chemoreflex in rats subjected to chronic stress

2020 ◽  
Author(s):  
Egidi Mayara Silva Firmino ◽  
Luciana Bärg Kuntze ◽  
Davi Campos Lagatta ◽  
Daniel Penteado Martins Dias ◽  
Leonardo Barbosa Moraes Resstel
Keyword(s):  
Cardiovascular Disease ◽  
Chronic Stress ◽  
Autonomic Function ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Male Rats ◽  
Cardiovascular Changes ◽  
Fluoxetine Treatment ◽  
Increased Risk ◽  
Repeated Restraint Stress

AbstractStress may influence the autonomic regulation, pathogenesis of cardiovascular disease and play an important role in animal behavior as depression. Depression is evidenced as a significant risk factor for cardiovascular changes. This is of great importance as some studies show an association between symptoms of depression and increased risk of cardiovascular disease (CVD) morbidity. Additionality, those alterations can be alleviated by use of antidepressants such as fluoxetine, which is a selective serotonin reuptake inhibitor (SSRIs). The link between depression and cardiovascular changes is known to be mediated in part by autonomic mechanisms that contribute to the regulation of cardiovascular function. However, studies on the effects of SSRIs on cardiovascular autonomic function are inconsistent. Thus, in the present study we investigated, in adult male rats, the effect of chronic and acute treatment with fluoxetine on changes in autonomic mechanisms of baroreflex and chemoreflex induced by the repeated restraint stress (RRS) or chronic variable stress (CVS) on baroreflex and chemoreflex in a protocol of 14 days of stress sessions. The results found demonstrated that exposure to chronic stress (RRS and CVS) promove changes on cardiovascular and ventilatory responses controlled by autonomic reflexes, such as baroreflex and chemoreflex. Additionality, that chronic fluoxetine treatment for 21 days was able to prevent not only anhedonic behavior, but also of autonomic changes cardiovascular induced by chronic stress. Taken together, our results show that pharmacological treatment with fluoxetine may be also helpful to prevent cardiovascular events on account of depressive states, by correcting alterations in autonomic function.

Physical Illness and Suicide Risk in Rural Residents of Contemporary China

Crisis ◽  
2014 ◽  
Vol 35 (5) ◽  
pp. 330-337 ◽  
Author(s):  
Cun-Xian Jia ◽  
Lin-Lin Wang ◽  
Ai-Qiang Xu ◽  
Ai-Ying Dai ◽  
Ping Qin
Keyword(s):  
Risk Factor ◽  
Family Income ◽  
Rural China ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Health Condition ◽  
Physical Illness ◽  
Rural Residents ◽  
Increased Risk ◽  
Study Population

Background: Physical illness is linked with an increased risk of suicide; however, evidence from China is limited. Aims: To assess the influence of physical illness on risk of suicide among rural residents of China, and to examine the differences in the characteristics of people completing suicide with physical illness from those without physical illness. Method: In all, 200 suicide cases and 200 control subjects, 1:1 pair-matched on sex and age, were included from 25 townships of three randomly selected counties in Shandong Province, China. One informant for each suicide or control subject was interviewed to collect data on the physical health condition and psychological and sociodemographic status. Results: The prevalence of physical illness in suicide cases (63.0%) was significantly higher than that in paired controls (41.0%; χ2 = 19.39, p < .001). Compared with suicide cases without physical illness, people who were physically ill and completed suicide were generally older, less educated, had lower family income, and reported a mental disorder less often. Physical illness denoted a significant risk factor for suicide with an associated odds ratio of 3.23 (95% CI: 1.85–5.62) after adjusted for important covariates. The elevated risk of suicide increased progressively with the number of comorbid illnesses. Cancer, stroke, and a group of illnesses comprising dementia, hemiplegia, and encephalatrophy had a particularly strong effect among the commonly reported diagnoses in this study population. Conclusion: Physical illness is an important risk factor for suicide in rural residents of China. Efforts for suicide prevention are needed and should be integrated with national strategies of health care in rural China.

scholarly journals Impact of established cardiovascular disease on 10-year death after coronary revascularization for complex coronary artery disease

2021 ◽  
Author(s):  
Rutao Wang ◽  
Scot Garg ◽  
Chao Gao ◽  
Hideyuki Kawashima ◽  
Masafumi Ono ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Coronary Revascularization ◽  
Long Term Outcomes ◽  
Vital Status ◽  
Increased Risk ◽  
Artery Disease ◽  
The Impact

Abstract Aims To investigate the impact of established cardiovascular disease (CVD) on 10-year all-cause death following coronary revascularization in patients with complex coronary artery disease (CAD). Methods The SYNTAXES study assessed vital status out to 10 years of patients with complex CAD enrolled in the SYNTAX trial. The relative efficacy of PCI versus CABG in terms of 10-year all-cause death was assessed according to co-existing CVD. Results Established CVD status was recorded in 1771 (98.3%) patients, of whom 827 (46.7%) had established CVD. Compared to those without CVD, patients with CVD had a significantly higher risk of 10-year all-cause death (31.4% vs. 21.7%; adjusted HR: 1.40; 95% CI 1.08–1.80, p = 0.010). In patients with CVD, PCI had a non-significant numerically higher risk of 10-year all-cause death compared with CABG (35.9% vs. 27.2%; adjusted HR: 1.14; 95% CI 0.83–1.58, p = 0.412). The relative treatment effects of PCI versus CABG on 10-year all-cause death in patients with complex CAD were similar irrespective of the presence of CVD (p-interaction = 0.986). Only those patients with CVD in ≥ 2 territories had a higher risk of 10-year all-cause death (adjusted HR: 2.99, 95% CI 2.11–4.23, p < 0.001) compared to those without CVD. Conclusions The presence of CVD involving more than one territory was associated with a significantly increased risk of 10-year all-cause death, which was non-significantly higher in complex CAD patients treated with PCI compared with CABG. Acceptable long-term outcomes were observed, suggesting that patients with established CVD should not be precluded from undergoing invasive angiography or revascularization. Trial registration SYNTAX: ClinicalTrials.gov reference: NCT00114972. SYNTAX Extended Survival: ClinicalTrials.gov reference: NCT03417050. Graphic abstract

scholarly journals 1487. Pneumonia due to Co-Infection in the ICU: Detection and Clinical Significance

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S745-S746
Author(s):  
Casey S Zelus ◽  
Michael Blaha ◽  
Kaeli Samsom ◽  
Jasmine R Marcelin ◽  
Trevor C Van Schooneveld ◽  
...  
Keyword(s):  
Clinical Significance ◽  
Diagnostic Testing ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Categorical Variables ◽  
Chi Square ◽  
Mechanically Ventilated ◽  
Critical Care Units ◽  
Outcomes Measures ◽  
The Impact

Abstract Background Pneumonia is a significant cause of morbidity and mortality, with increasing interest in the detection and clinical significance of co-infection. However, the impact of methodology to obtain lower respiratory samples along with the utility of various microbiological diagnostic testing remains unclear. Methods A single-center retrospective analysis was performed on bronchoalveolar lavage (BAL) samples obtained from mechanically ventilated adults treated in critical care units from August 2012 to December 2017. BAL methodology (bronchoscopic vs blinded), microbiological diagnostic testing, and outcomes measures were obtained. Associations between categorical variables were assessed using Chi-Square or Fisher’s exact tests. Kruskal Wallace tests analyzed differences in distributions of measures between categories based on number of organism types detected. SAS software version 9.4 (SAS Institute Inc., Cary, NC). Results Analysis of the 803 samples that met inclusion criteria found a significant linear association between mortality and number of organism types detected by BAL, with 30 day mortality rates of 43.0%, 47.8%, and 58.3% among those with zero, one, and two or more organisms respectively (p = 0.003). Comparing BALs with at least one organism isolated, the detection of viruses specifically was associated with increased mortality, with the presence and absence of viral organisms corresponding to 56.3% and 46.5% mortality at thirty days (p = 0.03). No association was found between mortality and isolation of acid-fast bacilli, bacteria, or fungi. Co-infection was detected more frequently among bronchoscopic BALs than blinded BALs (26.3% vs 8.6%, p &lt; 0.0001), with more viruses detected bronchoscopic BALs (41.9% vs 13.1%, p &lt; 0.0001), and more bacteria in blinded BALs (41.8% vs 33.0%, p = 0.01). 30 Day Mortality vs Isolation of Specific Organism Types from BAL Number of Organism Types Isolated from BAL Compared to BAL Methodology BAL Methodology vs Isolation of Specific Organism Types Conclusion Co-infection in mechanically ventilated adult patients with pneumonia appears to be a significant risk factor for mortality, with the detection of viral organisms potentially playing an independent role. Within this population, bronchoscopic BALs may have a valuable diagnostic and prognostic methodology. Disclosures All Authors: No reported disclosures

Abstract P253: Proton Pump Inhibitor Use is Positively Associated with Incidence of Cardiovascular Disease

Circulation ◽  
2017 ◽  
Vol 135 (suppl_1) ◽  
Author(s):  
Elizabeth J Bell ◽  
Jennifer L St. Sauver ◽  
Veronique L Roger ◽  
Nicholas B Larson ◽  
Hongfang Liu ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiovascular Disease ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Language Processing ◽  
Proton Pump ◽  
Hazard Ratio ◽  
Time Varying ◽  
Increased Risk ◽  
The Impact

Introduction: Proton pump inhibitors (PPIs) are used by an estimated 29 million Americans. PPIs increase the levels of asymmetrical dimethylarginine, a known risk factor for cardiovascular disease (CVD). Data from a select population of patients with CVD suggest that PPI use is associated with an increased risk of stroke, heart failure, and coronary heart disease. The impact of PPI use on incident CVD is largely unknown in the general population. Hypothesis: We hypothesized that PPI users have a higher risk of incident total CVD, coronary heart disease, stroke, and heart failure compared to nonusers. To demonstrate specificity of association, we additionally hypothesized that there is not an association between use of H 2 -blockers - another commonly used class of medications with similar indications as PPIs - and CVD. Methods: We used the Rochester Epidemiology Project’s medical records-linkage system to identify all residents of Olmsted County, MN on our baseline date of January 1, 2004 (N=140217). We excluded persons who did not grant permission for their records to be used for research, were <18 years old, had a history of CVD, had missing data for any variable included in our model, or had evidence of PPI use within the previous year.We followed our final cohort (N=58175) for up to 12 years. The administrative censoring date for CVD was 1/20/2014, for coronary heart disease was 8/3/2016, for stroke was 9/9/2016, and for heart failure was 1/20/2014. Time-varying PPI ever-use was ascertained using 1) natural language processing to capture unstructured text from the electronic health record, and 2) outpatient prescriptions. An incident CVD event was defined as the first occurrence of 1) validated heart failure, 2) validated coronary heart disease, or 3) stroke, defined using diagnostic codes only. As a secondary analysis, we calculated the association between time-varying H 2 -blocker ever-use and CVD among persons not using H 2 -blockers at baseline. Results: After adjustment for age, sex, race, education, hypertension, hyperlipidemia, diabetes, and body-mass-index, PPI use was associated with an approximately 50% higher risk of CVD (hazard ratio [95% CI]: 1.51 [1.37-1.67]; 2187 CVD events), stroke (hazard ratio [95% CI]: 1.49 [1.35-1.65]; 1928 stroke events), and heart failure (hazard ratio [95% CI]: 1.56 [1.23-1.97]; 353 heart failure events) compared to nonusers. Users of PPIs had a 35% greater risk of coronary heart disease than nonusers (95% CI: 1.13-1.61; 626 coronary heart disease events). Use of H 2 -blockers was also associated with a higher risk of CVD (adjusted hazard ratio [95% CI]: 1.23 [1.08-1.41]; 2331 CVD events). Conclusions: PPI use is associated with a higher risk of CVD, coronary heart disease, stroke and heart failure. Use of a drug with no known cardiac toxicity - H 2 -blockers - was also associated with a greater risk of CVD, warranting further study.

scholarly journals The impact of levothyroxine exposure on delivery outcome in hypothyroid pregnant women (PETAL study): A five-year retrospective cohort study

2021 ◽  
pp. 1753495X2110641
Author(s):  
Diana Oprea ◽  
Nadine Sauvé ◽  
Jean-Charles Pasquier
Keyword(s):  
Cohort Study ◽  
Pregnant Women ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Caesarean Delivery ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Singleton Pregnancy ◽  
Delivery Outcome ◽  
The Impact

Background Hypothyroidism affects 3% of pregnant women, and to date, no studies have addressed the impact levothyroxine-treated hypothyroidism on delivery outcome. Methods This retrospective cohort study was conducted among 750 women with a singleton pregnancy who gave birth between 2015 and 2019. Delivery modes were compared between 250 hypothyroid women exposed to levothyroxine and 500 euthyroid control women. The aim of this study was to determine the impact of levothyroxine exposure on delivery outcome. Results Multiple logistic regression showed no significant association between exposure to levothyroxine and the overall rate of caesarean delivery (aOR 1.1; 95% CI 0.8 to 1.6). Mean TSH concentrations were significantly higher throughout the pregnancy in hypothyroid women despite levothyroxine treatment. Maternal and neonatal outcomes in both groups were not different. Conclusion Hypothyroidism treated with levothyroxine during pregnancy according to local guidelines is not a significant risk factor for caesarean delivery.

scholarly journals Obesity Does Not Increase Mortality after Emergency Surgery

2014 ◽  
Vol 2014 ◽  
pp. 1-3 ◽  
Author(s):  
Paula Ferrada ◽  
Rahul J. Anand ◽  
Ajai Malhotra ◽  
Michel Aboutanos
Keyword(s):  
Wound Infection ◽  
Emergency Surgery ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Patient Characteristics ◽  
Obese Patients ◽  
Exact Test ◽  
Icu Admission ◽  
Nonobese Patients ◽  
The Impact

Objective.The aim of this study is to evaluate the impact of obesity on patient outcomes after emergency surgery.Methods.A list of all patients undergoing emergent general surgical procedures during the 12 months ending in July 2012 was obtained from the operating room log. A chart review was performed to obtain the following data: patient characteristics (age, gender, BMI, and preexisting comorbidities), indication for surgery, and outcomes (pulmonary embolus (PE), deep venous thrombosis (DVT), respiratory failure, ICU admission, wound infection, pneumonia, and mortality). Obesity was defined as a BMI over 25. Comparisons of outcomes between obese and nonobese patients were evaluated using Fischer’s exact test. Predictors of mortality were evaluated using logistic regression.Results.341 patients were identified during the study period. 202 (59%) were obese. Both groups were similar in age (48 for obese versus 47 for nonobese,P=0.42). Obese patients had an increased incidence of diabetes, (27% versus 7%,P<0.05), hypertension (52% versus 34%,P<0.05), and sleep apnea (0% versus 5%,P<0.05). There was a statistically significant increased incidence of postoperative wound infection (obese 9.9% versus nonobese 4.3%,P<0.05) and ICU admission (obese 58% versus nonobese 42%,P=0.01) among the obese patients. Obesity alone was not shown to be a significant risk factor for mortality.Conclusions.A higher BMI is not an independent predictor of mortality after emergency surgery. Obese patients are at a higher risk of developing wound infections and requiring ICU admission after emergent general surgical procedure.

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