Peroxisome proliferator-activated receptors (PPARs) are fatty acid-activated transcription factors of nuclear hormone receptor superfamily that regulate energy metabolism. Currently, three PPAR ...subtypes have been identified: PPARα, PPARγ, and PPARβ/δ. PPARα and PPARδ are highly expressed in oxidative tissues and regulate genes involved in substrate delivery and oxidative phosphorylation (OXPHOS) and regulation of energy homeostasis. In contrast, PPARγ is more important in lipogenesis and lipid synthesis, with highest expression levels in white adipose tissue (WAT). In addition to tissues regulating whole body energy homeostasis, PPARs are expressed in immune cells and have an emerging critical role in immune cell differentiation and fate commitment. In this review, we discuss the actions of PPARs in the function of the innate and the adaptive immune system and their implications in immune-mediated inflammatory conditions.
•PPAR in the function on innate immune cells•PPAR function on adaptive immune cells•PPAR role in immune-mediated inflammatory conditions•PPAR therapeutic options in immunology
A 31-year-old Asian male never-smoker living in the upper Midwest with a past medical history of congenital bilateral hearing loss sought treatment with a 1-week history of fever, fatigue, ...right-sided pleuritic chest pain, shortness of breath, productive cough with mild intermittent hemoptysis, night sweats, and unintentional 10-lb weight loss over 4 weeks. He was adopted from South Korea as an infant, and thus the family history was unknown. He worked in the heating, ventilation, and air conditioning business, performing installations and repairs. There was no known exposure to animals, caves, rivers, lakes, or wooded areas. He travelled to South Korea and New Hampshire approximately 9 months previously. He did not take any medication.
Patients with cancer represent a particularly vulnerable population at risk of adverse outcomes related to COVID-19. Collectively, the initial studies, including patients with and without cancer, ...confirmed that patients with cancer had a higher risk of complications and death related to COVID-19. Subsequent studies on patients with COVID-19 and cancer investigated patient and disease-related factors associated with COVID-19 severity and morality. Multiple interconnected factors include demographics, comorbidities, cancer-associated variables, treatment side effects, and other parameters. However, there is a lack of clarity on the contributions of any one factor. In this commentary, we deconvolute the data of specific risk factors associated with worse outcomes due to COVID-19 in cancer patients and focus on understanding the recommended guidelines to mitigate COVID-19 risk in this vulnerable population. In the first section, we highlight the key parameters, including age and race, cancer status, type of malignancy, cancer therapy, smoking status and comorbidities that impact outcomes for cancer patients with COVID-19. Next, we discuss efforts made at the patient, health system, and population levels to mitigate the effects of the ongoing outbreak for patients with cancer, including (1) screening, barrier and isolation strategies (2), Masking/PPE (3), vaccination, and (4) systemic therapies (e.g., evusheld) to prevent disease onset in patients. In the last section, we discuss optimal treatment strategies for COVID-19, including additional therapies for patients with COVID-19 and cancer. Overall, this commentary focuses on articles with high yield and impact on understanding the evolving evidence of risk factors and management guidelines in detail. We also emphasize the ongoing collaboration between clinicians, researchers, health system administrators and policymakers and how its role will be important in optimizing care delivery strategies for patients with cancer. Creative patient-centered solutions will be critical in the coming years, post the pandemic.
A 39-year-old woman with systemic lupus erythematosus that was complicated by end-stage renal disease that had required a deceased donor renal transplant 16 years ago was referred for evaluation of ...chronic, nonproductive cough for 2 years. She was a lifetime nonsmoker whose condition was maintained on prednisone 5 mg daily, tacrolimus 3 mg twice day, mycophenolate mofetil 500 mg twice a day for her immunosuppression regimen, valacyclovir 500 mg twice a day for prophylaxis, and clonidine 0.1 mg daily and metoprolol succinate 100 mg twice daily for hypertension.
Background Leukemia contributes significantly to the global cancer burden. Due to the importance of evaluating improvements in leukemia outcomes, the current study aimed to examine the variations in ...mortality-to-incidence ratio (MIR) between genders and association of MIR with the health expenditures in selected countries. Methods The leukemia incidence and mortality rates were extracted from the GLOBOCAN 2020 database. In total, 56 countries were included based on the data quality reports and the exclusion of missing data. The associations of MIR and changes in MIR over time (formula omittedMIR) with the human development index (HDI), current health expenditure (CHE) per capita, and current health expenditure as a percentage of gross domestic product (CHE/GDP) were investigated using Spearman's rank correlation coefficient. Results In 2020, an estimated 474,519 new cases of leukemia were diagnosed globally, and 311,594 deaths occurred due to the disease. Male patients exhibited a higher incidence and mortality of leukemia compared to females on a global scale. Our analysis revealed that the MIRs were the highest and lowest in Egypt (0.79) and the United States (0.29), respectively. Remarkably, countries with greater HDI, higher CHE per capita, and a higher CHE/GDP tended to have lower MIR in both genders and within gender-specific subgroups. The deltaMIR demonstrated a significant negative correlation with HDI and CHE per capita, whereas no significant associations were observed among female patients for CHE/GDP. Besides, all three indicators showed trends towards negative correlations with deltaMIR among males, though these trends were not statistically significant (p0.05). Conclusions Generally, leukemia MIRs tended to be most favorable (i.e., lower) in countries with high HDI and high health expenditure. The gender differences observed in leukemia outcomes may reflect the potential influence of social, material, behavioral, and biological factors. Keywords: Leukemia, Incidence, Mortality, Mortality-to-incidence ratio, GLOBOCAN 2020
In recent decades, variability in the incidence and mortality of kidney cancer (KC) has been reported. This study aimed to compare trends in incidence, mortality, and disability-adjusted life years ...(DALY) of KC between the European Union (EU) 15 + countries and 6 World Health Organization (WHO) regions. The data of KC Age-standardized incidence rates (ASIRs), age-standardized mortality rates (ASMRs), and age-standardized DALYs were extracted from the Global Burden of Disease database. Joinpoint regression was employed to examine trends. From 1990 to 2019, the ASIR increased in most countries except for Luxembourg (males), the USA (females) and Austria and Sweden (both sexes). ASIR increased across all 6 WHO regions for both sexes except for females in Americas. The ASMR increased in 10/19 countries for males and 9/19 for females as well across most WHO regions. The mortality-to-incidence ratio (MIR) decreased in all countries and WHO regions. Trends in DALYs were variable across countries and WHO regions. While the incidence and mortality from KC rose in most EU15 + countries and WHO regions from 1990 to 2019, the universal drop in MIR suggests an overall improvement in KC outcomes. This is likely multifactorial, including earlier detection of KC and improved treatments.
The incidence of colorectal cancer (CRC) in the U.S. is declining in adults 50 years and older; however, recent studies suggest an increasing disease burden among adults under age 50. This study aims ...to compare the incidence, mortality, and mortality-to-incidence ratios (MIRs) of CRC in EU15+ countries to determine if similar age-stratified occurrences are observed across these countries with similar “Western lifestyle”-related risk factors. Incidence and mortality rates for CRC between 1990 and 2019 were extracted using the Global Burden of Disease database. The data were age-stratified into groups between ages 25–49, 50–69, and greater than 69 years. We observed that the incidence of CRC increased globally for all age groups, with the highest increase observed for males (75.9%) and females (27.7%) aged 25–49. A similar trend was observed in 15 of the 19 EU15+ countries for males and 16 of the 19 EU15+ countries for females aged 25–49. Global mortality rates decreased for all age groups in females but increased for males in all age groups. This raises concerns regarding potentially modifiable risk factors contributing to increased CRC development and underscores the importance of implementing standardized screening at an earlier stage to ensure adequate detection in the younger population.
Abstract
Cystic fibrosis transmembrane conductance regulator modulators have revolutionized cystic fibrosis (CF) care in the past decade. This study explores the CF-related mortality trends in the US ...from 1999 to 2020. We extracted CF-related mortality data from the CDC WONDER database. CF age-standardized mortality rates (ASMRs) were identified by ICD-10 code E84 and were stratified by demographic and geographical variables. Temporal trends were analyzed using Joinpoint modeling. CF-related ASMRs decreased from 1.9 to 1.04 per million population (
p
= 0.013), with a greater reduction in recent years. This trend was replicated in both sexes. The median age of death increased from 24 to 37 years. CF mortality rates decreased across sex, white race, non-Hispanic ethnicity, census regions, and urbanization status. Incongruent trends were reported in non-white races and Hispanic ethnicity. A lower median age of death was observed in women, non-white races, and Hispanic ethnicity. SARS-CoV-2 infection was the primary cause of death in 1.7% of CF decedents in 2020. The national CF-related mortality rates declined and the median age of death among CF decedents increased significantly indicating better survival in the recent years. The changes were relatively slow during the earlier period of the study, followed by a greater decline lately. We observed patterns of sex, ethnic, racial, and geographical disparities associated with the worsening of the gap between ethnicities, narrowing of the gap between races and rural vs. urban counties, and closing of the gap between sexes over the study period.
Abstract The global incidence of gout has increased rapidly, likely secondary to the increase in the prevalence of conditions that predispose to gout, such as obesity. Depending on the population ...studied, the prevalence of gout ranges from less than 1 to 6.8%. Thus, gout can be a significant burden on healthcare systems. The objective of this study is to observe the trends in the incidence, prevalence, and disability-adjusted life years (DALYs) of gout between 1990 and 2019 globally and in the European Union (EU) 15+ nations. We extracted data from the Global Burden of Disease Study database based on the International Classification of Diseases (ICD) versions 10 and 9. Incidence, prevalence, and disability-adjusted life years (DALYs) were extracted for individual EU15+ countries and globally in males and females between 1990 and 2019. Joinpoint regression analysis was used to describe trends. Between 1990 and 2019, gout prevalence, incidence, and DALYs increased in both males (+ 21.42%, + 16.87%, + 21.49%, respectively) and females (+ 21.06%, + 18.75%, + 20.66%, respectively) globally. The United States of America had the highest increase in prevalence (males: + 90.6%; females + 47.1%), incidence (males: + 63.73%; females: + 39.11%) and DALYs (males: + 90.43%; females: + 42.75%). Incidence, prevalence, and DALYs from gout are increasing worldwide and in most of the EU15+ countries for males and females. Studies have reported the association of gout with comorbidities such as metabolic syndrome, diabetes mellitus, and cardiovascular disease. Health policies and resource allocation are required to increase awareness and modify risk factors globally.
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