Pub Date : 2024-01-01Epub Date: 2024-04-26DOI: 10.26502/aimr.0168
Vinitha Deepu, Vikrant Rai, Devendra K Agrawal
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.
{"title":"Quantitative Assessment of Intracellular Effectors and Cellular Response in RAGE Activation.","authors":"Vinitha Deepu, Vikrant Rai, Devendra K Agrawal","doi":"10.26502/aimr.0168","DOIUrl":"10.26502/aimr.0168","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":519871,"journal":{"name":"Archives of internal medicine research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11113086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141089592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01Epub Date: 2024-06-04DOI: 10.26502/aimr.0170
Fihr Chaudhary, Devendra K Agrawal
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.
{"title":"Ethnic and Racial Disparities in Clinical Manifestations of Atopic Dermatitis.","authors":"Fihr Chaudhary, Devendra K Agrawal","doi":"10.26502/aimr.0170","DOIUrl":"https://doi.org/10.26502/aimr.0170","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":519871,"journal":{"name":"Archives of internal medicine research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11210272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141474489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01Epub Date: 2024-02-16DOI: 10.26502/aimr.0163
Hassan Ashktorab, Antonio Pizuorno, Lakshmi Gayathri Chirumamilla, Folake Adeleye, Maryam Mehdipour Dalivand, Zaki A Sherif, Gholamreza Oskrochi, Suryanarayana Reddy Challa, Boubini Jones-Wonni, Sheldon Rankine, Chiamaka Ekwunazu, Abigail Banson, Rachel Kim, Chandler Gilliard, Elizabeth Ekpe, Nader Shayegh, Constance Nyaunu, Chidi Martins, Ashley Slack, Princess Okwesili, Malachi Abebe, Yashvardhan Batta, Do Ly, Ogwo Valarie, Tori Smith, Kyra Watson, Oluwapelumi Kolawole, Sarine Tahmazian, Sofiat Atoba, Myra Khushbakht, Gregory Riley, Warren Gavin, Areeba Kara, Manuel Hache-Marliere, Leonidas Palaiodimos, Vishnu R Mani, Aleksandr Kalabin, Vijay Reddy Gayam, Pavani Reddy Garlapati, Joseph Miller, Fatimah Jackson, John M Carethers, Vinod Rustgi, Hassan Brim
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.
{"title":"African Americans Possessed High Prevalence of Comorbidities and Frequent Abdominal Symptoms, and Comprised A Disproportionate Share of Covid-19 Mortality among 9,873 Us- Hospitalized Patients Early in the Pandemic.","authors":"Hassan Ashktorab, Antonio Pizuorno, Lakshmi Gayathri Chirumamilla, Folake Adeleye, Maryam Mehdipour Dalivand, Zaki A Sherif, Gholamreza Oskrochi, Suryanarayana Reddy Challa, Boubini Jones-Wonni, Sheldon Rankine, Chiamaka Ekwunazu, Abigail Banson, Rachel Kim, Chandler Gilliard, Elizabeth Ekpe, Nader Shayegh, Constance Nyaunu, Chidi Martins, Ashley Slack, Princess Okwesili, Malachi Abebe, Yashvardhan Batta, Do Ly, Ogwo Valarie, Tori Smith, Kyra Watson, Oluwapelumi Kolawole, Sarine Tahmazian, Sofiat Atoba, Myra Khushbakht, Gregory Riley, Warren Gavin, Areeba Kara, Manuel Hache-Marliere, Leonidas Palaiodimos, Vishnu R Mani, Aleksandr Kalabin, Vijay Reddy Gayam, Pavani Reddy Garlapati, Joseph Miller, Fatimah Jackson, John M Carethers, Vinod Rustgi, Hassan Brim","doi":"10.26502/aimr.0163","DOIUrl":"https://doi.org/10.26502/aimr.0163","url":null,"abstract":"<p><strong>Background and aim: </strong>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.</p><p><strong>Design setting and participants: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":519871,"journal":{"name":"Archives of internal medicine research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11062622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140861622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01Epub Date: 2024-04-22DOI: 10.26502/aimr.0167
Jerry Trinh, Jennifer Shin, Vikrant Rai, Devendra K Agrawal
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. p27kip, 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 p27kip 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 p27kip, direct links necessitate further investigation. This critical review discusses the role of mTOR, p27kip, and OSM in VSMC proliferation and differentiation followed by the therapeutic potential of targeting these mediators in atherosclerosis to attenuate plaque vulnerability.
动脉粥样硬化是冠状动脉疾病的重要诱因,它包括胆固醇、纤维蛋白和脂质在动脉壁内的积聚,引发炎症反应,最终形成斑块。这种多方面的相互作用包括过度纤维化、脂肪斑块形成、血管平滑肌细胞(VSMC)增殖以及白细胞迁移对炎症途径的反应。稳定的斑块能抵御并发症的侵袭,而脆弱的斑块则会导致血栓形成、心肌梗死、中风和急性脑血管意外。VSMC 的细微表型受基因调控和环境因素的影响,仍然至关重要。α-SMA、肌球蛋白重链和钙蛋白等重要标志物可调节 VSMC 的迁移和收缩,但在 VSMC 脱分化和增殖过程中表达会减少。IL-6家族细胞因子Oncostatin M(OSM)与MMP上调和泡沫细胞形成有关,影响斑块的发展。以抑制哺乳动物雷帕霉素靶标(mTOR)为目标的研究,特别是使用雷帕霉素及其类似物,显示出了潜力,但由于相关的不良反应,也带来了挑战。探索 p27kip 对斑块巨噬细胞的影响是一条大有可为的途径,但其全部治疗潜力仍有待开发。同样,虽然 OSM 在通过 p27kip 诱导细胞周期停滞方面表现出了潜力,但直接的联系还需要进一步研究。这篇重要综述讨论了 mTOR、p27kip 和 OSM 在血管内皮细胞增殖和分化中的作用,以及针对动脉粥样硬化中这些介质的治疗潜力,以减轻斑块的脆弱性。
{"title":"Therapeutic Potential of Targeting p27<sup>kip1</sup> in Plaque Vulnerability.","authors":"Jerry Trinh, Jennifer Shin, Vikrant Rai, Devendra K Agrawal","doi":"10.26502/aimr.0167","DOIUrl":"10.26502/aimr.0167","url":null,"abstract":"<p><p>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<sup>kip</sup>, 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<sup>kip</sup> 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<sup>kip</sup>, direct links necessitate further investigation. This critical review discusses the role of mTOR, p27<sup>kip</sup>, and OSM in VSMC proliferation and differentiation followed by the therapeutic potential of targeting these mediators in atherosclerosis to attenuate plaque vulnerability.</p>","PeriodicalId":519871,"journal":{"name":"Archives of internal medicine research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11087066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140912249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01Epub Date: 2024-03-01DOI: 10.26502/aimr.0164
Donald J Alcendor, Patricia Matthews-Juarez, Duane Smoot, James E K Hildreth, Paul D Juarez
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.
{"title":"Ending of the COVID-19 Related Public and National Health Emergency Declarations: Implications for Medically Underserved Populations in Tennessee.","authors":"Donald J Alcendor, Patricia Matthews-Juarez, Duane Smoot, James E K Hildreth, Paul D Juarez","doi":"10.26502/aimr.0164","DOIUrl":"10.26502/aimr.0164","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":519871,"journal":{"name":"Archives of internal medicine research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11107971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141077411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01Epub Date: 2024-03-16DOI: 10.26502/aimr.0165
Yssel Mendoza Mari, Marcel P Fraix, Devendra K Agrawal
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.
{"title":"Pulmonary Fibrosis and Diabetes Mellitus: Two coins with the same face.","authors":"Yssel Mendoza Mari, Marcel P Fraix, Devendra K Agrawal","doi":"10.26502/aimr.0165","DOIUrl":"https://doi.org/10.26502/aimr.0165","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":519871,"journal":{"name":"Archives of internal medicine research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10994216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140871934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01Epub Date: 2024-05-09DOI: 10.26502/aimr.0169
Gaithrri Shanmuganathan, Devendra K Agrawal
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.
{"title":"Diabetes and Abdominal Aortic Aneurysm: Is the Protective Effect on AAA Due to Antidiabetic Medications Alone, Due to the Disease Alone, or Both?","authors":"Gaithrri Shanmuganathan, Devendra K Agrawal","doi":"10.26502/aimr.0169","DOIUrl":"10.26502/aimr.0169","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":519871,"journal":{"name":"Archives of internal medicine research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11156236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141285817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01Epub Date: 2024-07-29DOI: 10.26502/aimr.0172
Donald J Alcendor, Paul D Juarez, Aramandla Ramesh, Katherine Y Brown, Mohammad Tabatabai, Patricia Matthews-Juarez
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.
{"title":"A Scoping Review on the Impact of COVID 19 on Vulnerable Populations: LGBTQ+ Persons, Persons Experiencing Homelessness, and Migrant Farm Workers in the US.","authors":"Donald J Alcendor, Paul D Juarez, Aramandla Ramesh, Katherine Y Brown, Mohammad Tabatabai, Patricia Matthews-Juarez","doi":"10.26502/aimr.0172","DOIUrl":"https://doi.org/10.26502/aimr.0172","url":null,"abstract":"<p><strong>Purpose: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results and discussion: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":519871,"journal":{"name":"Archives of internal medicine research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11412071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142305765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01Epub Date: 2024-01-20DOI: 10.26502/aimr.0160
Sarah El-Nakeep, Samragnyi Madala, Anusha Chidharla, Balarama Krishna Surapaneni, Subhrajit Saha, Benjamin Martin, Anup Kasi
Background: Radical excision (RE) for rectal cancer carries a higher risk of mortality and morbidity, while local excision (LE) could decrease these postoperative risks. However, the long-term benefit of LE is still debatable.
Aim: To study the effectiveness of LE versus RE in T1 and T2 rectal cancer.
Methods: A systematic review and meta-analysis was conducted using key databases like PubMed and ClinicalTrials.gov. Only cohort studies and randomized controlled trials were included. RevMan 5.4 tool was used for data analysis. Both clinical and statistical heterogeneity of the studies were assessed, and I2 >75% was considered as highly heterogeneous. The primary outcomes being measured were 5-year overall survival (OS) and 5-year disease free survival (DFS). A subgroup analysis of patients with T1-only was also conducted, without adjuvant chemo/radiotherapy.
Results: A total of 18 studies were included for final meta-analysis. Four were RCTs, while the other 15 were retrospective cohort studies. One included study had data from both RCT and non-RCT study groups. Nine studies were multicentered or national studies while nine were unicentral.There was no difference in risk ratio (RR) between OS: RR 0.95, 95% Confidence Interval (CI) [0.91, 0.99] and DFS: RR 0.93, 95% CI [0.87, 1.01]. There were lower hazards ratios in OS: RR 1.41, 95% CI [1.14, 1.74] and DFS: RR 1.95, 95% CI [1.36, 2.78] with radical, as compared to LE. Lower recurrence rate was associated with RE. Random effect model was used due to clinical heterogeneity between studies (different surgical procedures, tumor staging, adjuvant chemo or radiotherapy).
Conclusions: LE for early-stage rectal cancer has lower 5-year OS and DFS than RE, with higher local recurrence rate. However, LE is associated with lower early postoperative mortality, morbidity and length of stay as compared to RE.
背景:直肠癌根治性切除术(RE)具有较高的死亡率和发病率风险,而局部切除术(LE)可降低这些术后风险。目的:研究在 T1 和 T2 直肠癌中局部切除术与根治术的有效性:方法:利用PubMed和ClinicalTrials.gov等主要数据库进行系统回顾和荟萃分析。仅纳入了队列研究和随机对照试验。数据分析使用 RevMan 5.4 工具。对研究的临床和统计异质性进行了评估,I2>75%被视为高度异质性。衡量的主要结果是5年总生存期(OS)和5年无病生存期(DFS)。此外,还对未进行辅助化疗/放疗的纯T1患者进行了亚组分析:最终荟萃分析共纳入了 18 项研究。其中 4 项为研究性临床试验,另外 15 项为回顾性队列研究。其中一项研究同时包含了研究性临床试验组和非研究性临床试验组的数据。9项研究为多中心或全国性研究,9项为单中心研究:OS: RR 0.95, 95% Confidence Interval (CI) [0.91, 0.99] 和 DFS: RR 0.93, 95% CI [0.87, 1.01]之间的风险比(RR)没有差异。OS 的危险比较低:与 LE 相比,根治术的危险比更低:OS:RR 1.41,95% CI [1.14,1.74] DFS:RR 1.95,95% CI [1.36,2.78]。RE的复发率较低。由于不同研究之间存在临床异质性(不同的手术方法、肿瘤分期、辅助化疗或放疗),因此采用了随机效应模型:结论:与RE相比,LE治疗早期直肠癌的5年OS和DFS较低,局部复发率较高。然而,与RE相比,LE的术后早期死亡率、发病率和住院时间较低。
{"title":"Radical versus Local Surgical Excision for Early Rectal Cancer: A Systematic Review and Meta-Analysis.","authors":"Sarah El-Nakeep, Samragnyi Madala, Anusha Chidharla, Balarama Krishna Surapaneni, Subhrajit Saha, Benjamin Martin, Anup Kasi","doi":"10.26502/aimr.0160","DOIUrl":"https://doi.org/10.26502/aimr.0160","url":null,"abstract":"<p><strong>Background: </strong>Radical excision (RE) for rectal cancer carries a higher risk of mortality and morbidity, while local excision (LE) could decrease these postoperative risks. However, the long-term benefit of LE is still debatable.</p><p><strong>Aim: </strong>To study the effectiveness of LE versus RE in T1 and T2 rectal cancer.</p><p><strong>Methods: </strong>A systematic review and meta-analysis was conducted using key databases like PubMed and ClinicalTrials.gov. Only cohort studies and randomized controlled trials were included. RevMan 5.4 tool was used for data analysis. Both clinical and statistical heterogeneity of the studies were assessed, and I<sup>2</sup> >75% was considered as highly heterogeneous. The primary outcomes being measured were 5-year overall survival (OS) and 5-year disease free survival (DFS). A subgroup analysis of patients with T1-only was also conducted, without adjuvant chemo/radiotherapy.</p><p><strong>Results: </strong>A total of 18 studies were included for final meta-analysis. Four were RCTs, while the other 15 were retrospective cohort studies. One included study had data from both RCT and non-RCT study groups. Nine studies were multicentered or national studies while nine were unicentral.There was no difference in risk ratio (RR) between OS: RR 0.95, 95% Confidence Interval (CI) [0.91, 0.99] and DFS: RR 0.93, 95% CI [0.87, 1.01]. There were lower hazards ratios in OS: RR 1.41, 95% CI [1.14, 1.74] and DFS: RR 1.95, 95% CI [1.36, 2.78] with radical, as compared to LE. Lower recurrence rate was associated with RE. Random effect model was used due to clinical heterogeneity between studies (different surgical procedures, tumor staging, adjuvant chemo or radiotherapy).</p><p><strong>Conclusions: </strong>LE for early-stage rectal cancer has lower 5-year OS and DFS than RE, with higher local recurrence rate. However, LE is associated with lower early postoperative mortality, morbidity and length of stay as compared to RE.</p>","PeriodicalId":519871,"journal":{"name":"Archives of internal medicine research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11008054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140867096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}