Archives of internal medicine research最新文献

The review delves into the methods for the quantitative assessment of intracellular effectors and cellular response of Receptor for Advanced Glycation End products (RAGE), a vital transmembrane receptor involved in a range of physiological and pathological processes. RAGE bind to Advanced Glycation End products (AGEs) and other ligands, which in turn activate diverse downstream signaling pathways that impact cellular responses such as inflammation, oxidative stress, and immune reactions. The review article discusses the intracellular signaling pathways activated by RAGE followed by differential activation of RAGE signaling across various diseases. This will ultimately guide researchers in developing targeted and effective interventions for diseases associated with RAGE activation. Further, we have discussed how PCR, western blotting, and microscopic examination of various molecules involved in downstream signaling can be leveraged to monitor, diagnose, and explore diseases involving proteins with unique post-translational modifications. This review article underscores the pressing need for advancements in molecular approaches for disease detection and management involving RAGE.

Atopic dermatitis is a heterogenous inflammatory skin illness that may last for long time and affect people of different racial and ethnic backgrounds. The condition primarily appears in infants and young children. There are people living with atopic dermatitis in every country and every ethnic group, although the frequency of the disease varies greatly. Due to the varied clinical presentations that atopic dermatitis can have, it can be challenging to characterize and diagnose the disease, particularly in adults. Nevertheless, there exists a dearth of information pertaining to the various presentations of atopic dermatitis among individuals from diverse racial and cultural groups. This critical review article offers a succinct and comprehensive overview of the current findings on the epidemiology of atopic dermatitis with regards to ethnic and racial disparities. The findings hold potential significance in advancing the development of targeted treatments for personalized medicine approaches and enhancing the quality of life for patients with atopy.

Background and aim: Identifying clinical characteristics and outcomes of different ethnicities in the US may inform treatment for hospitalized COVID-19 patients. Aim of this study is to identify predictors of mortality among US races/ethnicities.

Design setting and participants: We retrospectively analyzed de-identified data from 9,873 COVID-19 patients who were hospitalized at 15 US hospital centers in 11 states (March 2020-November 2020). Main Outcomes and Measures: The primary outcome was to identify predictors of mortality in hospitalized COVID-19 patients.

Results: Among the 9,873 patients, there were 64.1% African Americans (AA), 19.8% Caucasians, 10.4% Hispanics, and 5.7% Asians, with 50.7% female. Males showed higher in-hospital mortality (20.9% vs. 15.3%, p=0.001). Non- survivors were significantly older (67 vs. 61 years) than survivors. Patients in New York had the highest in-hospital mortality (OR=3.54 (3.03 - 4.14)). AA patients possessed higher prevalence of comorbidities, had longer hospital stay, higher ICU admission rates, increased requirement for mechanical ventilation and higher in-hospital mortality compared to other races/ethnicities. Gastrointestinal symptoms (GI), particularly diarrhea, were more common among minority patients. Among GI symptoms and laboratory findings, abdominal pain (5.3%, p=0.03), elevated AST (n=2653, 50.2%, p=<0.001, OR=2.18), bilirubin (n=577, 12.9%, p=0.01) and low albumin levels (n=361, 19.1%, p=0.03) were associated with mortality. Multivariate analysis (adjusted for age, sex, race, geographic location) indicates that patients with asthma, COPD, cardiac disease, hypertension, diabetes mellitus, immunocompromised status, shortness of breath and cough possess higher odds of in-hospital mortality. Among laboratory parameters, patients with lymphocytopenia (OR2=2.50), lymphocytosis (OR2=1.41), and elevations of serum CRP (OR2=4.19), CPK (OR2=1.43), LDH (OR2=2.10), troponin (OR2=2.91), ferritin (OR2=1.88), AST (OR2=2.18), D-dimer (OR2=2.75) are more prone to death. Patients on glucocorticoids (OR2=1.49) and mechanical ventilation (OR2=9.78) have higher in-hospital mortality.

Conclusion: These findings suggest that older age, male sex, AA race, and hospitalization in New York were associated with higher in-hospital mortality rates from COVID-19 in early pandemic stages. Other predictors of mortality included the presence of comorbidities, shortness of breath, cough elevated serum inflammatory markers, altered lymphocyte count, elevated AST, and low serum albumin. AA patients comprised a disproportionate share of COVID-19 death in the US during 2020 relative to other races/ethnicities.

Atherosclerosis, a critical contributor to coronary artery diseases, involves the accumulation of cholesterol, fibrin, and lipids within arterial walls, inciting inflammatory reactions culminating in plaque formation. This multifaceted interplay encompasses excessive fibrosis, fatty plaque development, vascular smooth muscle cell (VSMC) proliferation, and leukocyte migration in response to inflammatory pathways. While stable plaques demonstrate resilience against complications, vulnerable ones, with lipid-rich cores, necrosis, and thin fibrous caps, lead to thrombosis, myocardial infarction, stroke, and acute cerebrovascular accidents. The nuanced phenotypes of VSMCs, modulated by gene regulation and environmental cues, remain pivotal. Essential markers like alpha-SMA, myosin heavy chain, and calponin regulate VSMC migration and contraction, exhibiting diminished expression during VSMC de-differentiation and proliferation. p27^kip, a CDK inhibitor, shows promise in regulating VSMC proliferation and appears associated with TNF-α-induced pathways impacting unstable plaques. Oncostatin M (OSM), an IL-6 family cytokine, correlates with MMP upregulation and foam cell formation, influencing plaque development. Efforts targeting mammalian target of rapamycin (mTOR) inhibition, notably using rapamycin and its analogs, demonstrate potential but pose challenges due to associated adverse effects. Exploration of the impact of p27^kip impact on plaque macrophages presents promising avenues, yet its complete therapeutic potential remains untapped. Similarly, while OSM has exhibited potential in inducing cell cycle arrest via p27^kip, direct links necessitate further investigation. This critical review discusses the role of mTOR, p27^kip, and OSM in VSMC proliferation and differentiation followed by the therapeutic potential of targeting these mediators in atherosclerosis to attenuate plaque vulnerability.

The Biden administration decided to end the COVID-19 National and Public Health emergencies on May 11, 2023. These emergency declarations were established by the Trump Administration in early 2020. Under the COVID-19 emergency declarations, US citizens were provided with COVID-19 testing, vaccines, and treatments at little or no cost. The declarations allowed the federal government the option of waiving and or modifying government programs such Medicare, Medicaid. The emergency declarations were directly tied to other COVID-19 related provisions that have also expired that includes Economic Security (CARES) Act, the American Rescue Plan Act (ARPA), the Families First Coronavirus Response Act (FFCRA), the Coronavirus Aid, Relief, and the Inflation Reduction Act (IRA), the Consolidated Appropriations Act, 2023 (CAA). In addition, there were other federal and state emergency programs that were provided and too numerous to report here. At the time of this writing, the state of Tennessee continues to have moderate and sporadic spikes in COVID-19 cases and hospitalizations. Tennessee has higher than the national average of uninsured and underinsured people in the US. In Tennessee, more than 600,000 people are uninsured or underinsured in 2023 according to a study by the Kaiser Family Foundation. The ending of the PHE greatly impact coverage, cost, and access to COVID related services that will disproportionately affect the uninsured and medically underserved populations in Tennessee, the south in general, and throughout the US. Medically underserved populations are those groups with disparities in primary care, living in poverty, older, or having higher than expected infant mortality.

Idiopathic pulmonary fibrosis (IPF) constitutes a long-term disease with a complex pathophysiology composed of multiple molecular actors that lead to the deposition of extracellular matrix, the loss of pulmonary function and ultimately the patient's death. Despite the approval of pirfenidone and nintedanib for the treatment of the disease, lung transplant is the only long-term solution to fully recover the respiratory capacity and gain quality of life. One of the risk factors for the development of IPF is the pre-existing condition of diabetes mellitus. Both, IPF and diabetes mellitus, share similar pathological damage mechanisms, including inflammation, endoplasmic reticulum stress, mitochondrial failure, oxidative stress, senescence and signaling from glycated proteins through receptors. In this critical review article, we provide information about this interrelationship, examining molecular mediators that play an essential role in both diseases and identify targets of interest for the development of potential drugs. We review the findings of clinical trials examining the progression of IPF and how novel molecules may be used to stop this process. The results highlight the importance of early detection and addressing multiple therapeutic targets simultaneously to achieve better therapeutic efficacy and potentially reverse lung fibrosis.

Metabolic Syndrome (MetS) is a complex cluster of metabolic irregularities that significantly increase the risk of developing chronic conditions, such as hypertension, type 2 diabetes, cardiovascular diseases, and other related disorders. This review aims to provide a comprehensive overview of the current understanding of MetS, its etiology and underlying pathogenesis, and the management strategies. MetS is characterized by central obesity, high blood pressure, insulin resistance, hyperglycemia, hypertriglyceridemia, and low high-density lipoprotein cholesterol levels. The prevalence of MetS is remarkably high, affecting approximately 25% of the global population, particularly in developed nations with inactive lifestyles and high-calorie diets. The development of MetS involves genetic and acquired factors, resulting in an inflammatory state that enhances the risk for cardiovascular disease. The biochemical alterations observed in MetS establish pathological connections between MetS, diabetes, and cardiovascular and neurodegenerative conditions. Despite its clinical importance, there is still debate regarding the precise components and pathophysiological associations among MetS elements. However, advancements in therapeutic measures, including drug therapies, surgical options, and experimental methods present promising avenues for managing and potentially reversing MetS. Further investigation of the MetS is critical because of its significant implications for public health and its connection to other clinical conditions and severe health outcomes, placing a substantial burden on healthcare system and society.

Arteriovenous fistula (AVF) is a surgical connection between an artery and a vein created in patients with end-stage renal disease needing dialysis. A major concern with AVF is maturation failure which results, while creating a new AVF, a troublesome process for the patients. Thus, maturation of AVF is important which is achieved by outflow tract outward remodeling. However, vessel stenosis, hypoxia, endothelial dysfunction, and thrombosis contribute to AVF failure. Vascular stenosis and thrombosis after intimal injury due to intimal hyperplasia followed by plaque formation are major factors contributing to AVF maturation failure. Angiogenesis during plaque formation is important and plays a critical role but is also involved in vessel stenosis if uncontrolled. This suggests the dual role of angiogenesis and its effects on AVF maturation. Thus, it is critical to understand the factors regulating neoangiogenesis after the creation of AVF. Not only the angiogenesis in the plaque area but also in the adjoining tissues including muscles due to injury and the factors released by the perivascular structure may influence the angiogenesis and AVF maturation process. This review article comprehensively and critically discusses the role of neoangiogenesis in AVF maturation and the role of various factors regulating angiogenesis (pro- and anti-angiogenic factors) with their potential role in AVF maturation.

Diabetes is a metabolic disease that may result in multiple microvascular and macrovascular diseases. Interestingly, many studies have demonstrated the inverse relationship between diabetes and the development and expansion of abdominal aortic aneurysm (AAA). One hypothesis is that the aortic wall stiffness resulting from hyperglycemia and advanced glycation end products could delay the development and growth of AAA. Other studies have proposed that the concurrent use of antidiabetic medications which promote anti-inflammatory cytokines while hindering pro-inflammatory cytokines may potentially be the reason for this protective effect of diabetes on AAA. Contrastingly, the presence of diabetes has been found to have a negative effect on the outcome of AAA following its repair which may be due to elevated blood glucose negatively affecting the healing process. The current literature has also demonstrated the negative impact of the use of fluoroquinolones on AAA. This comprehensive review critically reviewed and summarized the role of diabetes, anti-diabetes medications and fluoroquinolones on AAA, and on the effect of diabetes and certain anti-diabetes medications on outcomes following its repair.

Purpose: The goal of the National Center for Medical Education Development and Research Center (NCMEDR) is to support the education and training of medical students in the care of vulnerable populations. Access to primary care services in the US is fundamental to the health and wellness of all people regardless of their socioeconomic status. LGBQ+ persons, (lesbian, gay, bisexual, transgender, queer, and other sexual and gender minority), Persons Experiencing Homelessness (PEH), and Migrant Farm Workers (MFW) are among the most underserved, marginalized, and socially vulnerable groups in the US. NCMEDR in the Department of Family and Community Medicine at Meharry Medical College was established in part, with funding from the Department of Health and Human Services (DHHS) and the Health Resources and Services Administration (HRSA). NCMEDR was developed to provide educational pathways for transforming medical education and clinical practice in the US by ascertaining whether medical students were being trained to provide primary care, and behavioral health services to LGBTQ+ persons, PEH, and MFW. Here we focus on the impact of the COVID-19 pandemic on these specific populations because they represent marginalized groups that have been heavily impacted by the pandemic, have poor social determinants of health (SDOH), and are more likely to be uninsured, and are less likely to engage primary care providers outside of emergency room care.

Methods: In this study, a scoping literature review was conducted to assess the impact of COVID-19 on primary care of LQBTQ+ persons, PEH, and MFW.

Results and discussion: The pandemic provided a serious health disparities gap for the defined vulnerable populations under review by the NCMEDR. The pandemic identified the need for transformative measures for clinical practices, medical education, and health care policies required for implementation to improve health care for vulnerable groups. We make recommendations for interventions with defined populations that may influence clinical, environmental health, and SDOH in the COVID era.

Conclusions: The COVID pandemic directed the need for medical schools, health care and social organizations to intervene in new and different ways in vulnerable and marginalized communities. The recommendations provide a model for advancing health equity, access, quality, utilization, care coordination, and treatment.