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The ERBB4 receptor tyrosine kinase promotes colonocyte survival. Herein, we tested whether ERBB4's antiapoptotic signaling promotes transformation and colorectal tumorigenesis. ERBB4 alterations in a The Cancer Genome Atlas colorectal cancer (CRC) data set stratified survival, and in a combined Moffitt Cancer Center and Vanderbilt Medical Center CRC expression data set, ERBB4 message levels were increased at all tumor stages. Similarly, western blot and immunohistochemistry on additional CRC tissue banks showed elevated ERBB4 protein in tumors. ERBB4 was highly expressed in aggressive, dedifferentiated CRC cell lines, and its knockdown in LIM2405 cells reduced anchorage-independent colony formation. In nude mouse xenograft studies, ERBB4 alone was insufficient to induce tumor establishment of non-transformed mouse colonocytes, but its over-expression in cells harboring Apc(min) and v-Ha-Ras caused a doubling of tumor size. ERBB4-expressing xenografts displayed increased activation of survival pathways, including epidermal growth factor receptor and Akt phosphorylation and COX-2 expression, and decreased apoptotic signals. Finally, ERBB4 deletion from mouse intestinal epithelium impaired stem cell replication and in vitro enteroid establishment. In summary, we report that ERBB4 is over-expressed in human CRC, and in experimental systems enhances the survival and growth of cells driven by Ras and/or WNT signaling. Chronic ERBB4 over-expression in the context of, for example, inflammation may contribute to colorectal carcinogenesis. Tumors with high receptor levels are likely to have enhanced cell survival signaling through epidermal growth factor receptor, PI3K and COX-2. These results suggest ERBB4 as a novel therapeutic target in a subset of CRC.
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Neoplasias Colorretais/patologia , Receptor ErbB-4/metabolismo , Animais , Diferenciação Celular , Linhagem Celular Tumoral , Sobrevivência Celular , Transformação Celular Neoplásica , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Neoplasias Colorretais/metabolismo , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Técnicas de Silenciamento de Genes , Humanos , Camundongos Nus , Receptor ErbB-4/genética , Análise Serial de Tecidos , Ensaios Antitumorais Modelo de Xenoenxerto , Proteínas ras/genética , Proteínas ras/metabolismoRESUMO
Activating mutations in KRAS occur in 30% to 40% of colorectal cancers. How mutant KRAS alters cancer cell behavior has been studied intensively, but non-cell autonomous effects of mutant KRAS are less understood. We recently reported that exosomes isolated from mutant KRAS-expressing colon cancer cells enhanced the invasiveness of recipient cells relative to exosomes purified from wild-type KRAS-expressing cells, leading us to hypothesize mutant KRAS might affect neighboring and distant cells by regulating exosome composition and behavior. Herein, we show the results of a comprehensive proteomic analysis of exosomes from parental DLD-1 cells that contain both wild-type and G13D mutant KRAS alleles and isogenically matched derivative cell lines, DKO-1 (mutant KRAS allele only) and DKs-8 (wild-type KRAS allele only). Mutant KRAS status dramatically affects the composition of the exosome proteome. Exosomes from mutant KRAS cells contain many tumor-promoting proteins, including KRAS, EGFR, SRC family kinases, and integrins. DKs-8 cells internalize DKO-1 exosomes, and, notably, DKO-1 exosomes transfer mutant KRAS to DKs-8 cells, leading to enhanced three-dimensional growth of these wild-type KRAS-expressing non-transformed cells. These results have important implications for non-cell autonomous effects of mutant KRAS, such as field effect and tumor progression.
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Neoplasias do Colo/química , Neoplasias do Colo/patologia , Exossomos/química , Invasividade Neoplásica , Proteínas de Neoplasias/química , Proteoma/química , Proteínas Proto-Oncogênicas/química , Proteínas ras/química , Alelos , Linhagem Celular Tumoral , Proliferação de Células , Cromatografia Líquida , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Exossomos/metabolismo , Humanos , Mutação , Proteínas de Neoplasias/metabolismo , Transporte Proteico , Proteoma/metabolismo , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas p21(ras) , Transdução de Sinais , Espectrometria de Massas em Tandem , Microambiente Tumoral , Proteínas ras/genética , Proteínas ras/metabolismoRESUMO
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) comprises a spectrum of autoimmune diseases, including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). Studies have shown that avacopan and mepolizumab are promising therapeutics for partial or complete replacement of glucocorticoids (GC), with sustained remission while completely weaning off GC. Avacopan inhibits C5aR in the complement pathway, preventing neutrophil migration, while mepolizumab targets IL-5R, reducing eosinophil activity. Additionally, complement inhibition has not only contributed to the recovery of renal function and alleviation of physical symptoms but has also enhanced patients' overall quality of life and mental well-being. This systematic review explores the pathogenesis of AAV, traditional treatments, and the potential of emerging complement and interleukin antagonist therapies such as avacopan and mepolizumab in revolutionizing AAV management.
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Lactational infective mastitis (LIM) was previously thought to occur due to trapped milk causing inadequate milk drainage and consequent infection. However, advances in genome sequencing techniques have shown that the abundance of Staphylococcus aureus, Staphylococcus epidermidis, Lactobacilli species, and Bifidobacterium species in the breast milk of lactating women play a key role in the development of LIM. Recent discoveries have revealed that the breast milk microbiome is composed of bacteria and other microorganisms, which are seeded through multiple pathways and are influenced by maternal factors. An imbalance in the microbial abundance in breast milk can lead to LIM. Given that this infection can cause early termination of breastfeeding, it is imperative to discuss prevention and treatment options. The objective of this review is to highlight the pathogens involved in LIM affecting human mothers, routes of bacterial transfer, and contributing factors that may influence changes in the composition of the milk microbiota, as well as propose preventative and curative treatment options.
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Rheumatic diseases are a group of conditions including arthritis and various other conditions that can lead to chronic inflammation within the musculoskeletal system, which can have negative effects on soft tissues, bones, muscles, joints, and connective tissue. One form of arthritis is gout, which is an inflammatory condition in which urate acid crystals build up in joints. Gout is associated with joint swelling, pain, redness, and joint mobility issues. Early diagnosis and treatment are essential to prevent joint degradation and other adverse complications. The condition has been shown to increase the incidence of diseases outside the musculoskeletal system, including the renal and cardiovascular systems. Comorbid conditions associated with gout include but are not limited to type 2 diabetes mellitus (T2DM), hypertension, hyperlipidemia, chronic kidney disease, cardiovascular disease, and heart failure. This systematic review aims to provide insight into the relationship between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, uric acid levels, and gout.
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As cancer continues to be the leading cause of death worldwide, additional therapeutic options other than traditional platinum-based chemotherapy have become available that target tumor cells in innovative ways. Immunotherapies (e.g., immune checkpoint inhibitors (ICI)) ramp up the immune system to target cancer cells, providing patients with more personalized and tumor cell-specific treatment options. This new age oncological treatment option has been found to provide a more meaningful and stronger alternative to traditional chemotherapy, resulting in longer periods of remission and milder side effects. However, because ICI heightens the immune system, resultant autoimmune conditions can occur. One of the most recently shown adverse effects of ICI are extreme hyperglycemia (i.e., type 1 diabetes) and diabetic ketoacidosis (DKA). To determine the incidence of immunotherapy-induced diabetes, a systematic literature review was performed using CINHAL, EBSCO, MEDLINE, and Web of Science. A total of 403 articles were initially screened, with a final 28 case reports included. The results show that checkpoint inhibitors were found to be most commonly associated with new-onset diabetes as opposed to traditional chemotherapy. Additionally, 41% of patients developed autoimmune diabetes and DKA after being placed on a single therapy of pembrolizumab (targets PD-1: programmed cell death protein 1). However, the pathological process underlying the development of endocrinopathies after treatment with ICI continues to be under investigation.
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Ensuring access to proper eye health services is not only a fundamental human right but also crucial for preserving an individual's quality of life, preventing blindness, and promoting overall well-being. This is especially true in low-income countries like Sub-Saharan Africa (SSA) where recognizing the intricate relationship between access to healthcare and social determinants of health (SDOH ) is crucial to addressing health disparities. The goal of this study was to elucidate and highlight not only the barriers millions face in obtaining eye care but also pave the way for interventions and policies aimed at creating equitable access across diverse populations. To do this, a scoping review was conducted across the Cumulated Index to Nursing and Allied Health Literature (CINAHL), Embase, and PubMed databases for studies meeting the search terms and inclusion criteria. The results show that intervention strategies that increase vision care must extend beyond the healthcare sector to address the multifaceted challenges. Collaborating with stakeholders involved in addressing broader livelihood issues, such as food security, education, and SDOH, becomes imperative to ensure comprehensive and sustainable improvements in vision care accessibility in SSA.
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Probiotics have garnered increasing attention, particularly within the realm of atopic dermatitis (AD). Although classified as dietary supplements by the Food and Drug Administration, probiotics are being explored for their potential to modify immune system responses and aid in disease recovery. This review aims to provide a current understanding of probiotics, specifically various lactobacilli strains, as a therapeutic option in preventing and treating AD. The concept of the gut-skin axis has gained substantial recognition, emphasizing the complex relationship between the gut microbiome and skin health. Dysfunctional gut barriers and metabolites produced by gut microorganisms can exert profound influences on skin conditions, including AD. Lactobacilli species are particularly noteworthy for their resilience and stability within the gastrointestinal tract, making these bacteria ideal candidates for probiotic supplementation. Various lactobacilli strains (Lactobacillus salivarius, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus reuteri, and Lactobacillus rhamnosus) were included in this study due to their current uses in mitigating AD symptomatology. This systemic review article aims to shed light on the potential of probiotics as a therapeutic approach for AD, highlighting their stellar safety profile and promising therapeutic efficacy. Given the compelling preliminary findings and the constraints associated with conventional treatments, probiotics, particularly lactobacilli strains, emerge as a considerable alternative or adjuvant option for individuals grappling with AD. Further exploration is imperative to establish probiotics as a promising therapeutic option, providing renewed hope for those seeking effective strategies for managing AD.
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Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects multiple systems of the body. Recent research on the gut microbiota dysbiosis associated with SLE patients has gained traction and warranted further exploration. It has not been determined whether the change in the gut microbiota is a cause of SLE or a symptom of SLE. However, based on the physiological and pathophysiological role of the bacteria in the gut microbiome, as levels of the bacteria rise or fall, symptomatology in SLE patients could be affected. This review analyzes the recent studies that examined the changes in the gut microbiota of SLE patients and highlights the correlations between gut dysbiosis and the clinical manifestations of SLE. A systematic search strategy was developed by combining the terms "SLE," "systemic lupus erythematosus," and "gut microbiome." Biomedical Reference Collection, CINAHL, Medline ProQuest, and PubMed Central databases were searched by combining the appropriate keywords with "AND." Only full-text, English-language articles were searched. The articles were restricted from 2013 to 2023. Only peer-reviewed controlled studies with both human and animal trials were included in this scoping review. Review articles, non-English articles, editorials, case studies, and duplicate articles from the four databases were excluded.â¯Various species of bacteria were found to be positively or negatively associated with SLE gut microbiomes. Among the bacterial species increased were Clostridium, Lactobacilli, Streptococcus, Enterobacter, and Klebsiella. The bacterial species that decreased were Bifidobacteria, Prevotella, and the Firmicutes/Bacteroidetes ratio. Literature shows that Clostridium is one of several bacteria found in abundance, from pre-disease to the diseased state of SLE. Lachnospiraceae and Ruminococcaceae are both part of the family of butyrate-producing anaerobes that are known for their role in strengthening the skin barrier function and, therefore, may explain the cutaneous manifestations of SLE patients. Studies have also shown that the Firmicutes/Bacteroidetes ratio is significantly depressed, which may lead to appetite changes and weight loss seen in SLE patients. Based on the established role of these bacteria within the gut microbiome, the disruption in the gut ecosystem could explain the symptomatology common in SLE patients. By addressing these changes, our scoping review encourages further research to establish a true causal relationship between the bacterial changes in SLE patients as well as furthering the scope of microbiota changes in other systems and autoimmune diseases.
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Lyme disease is a tick-borne illness known for its ability to cause multi-systemic manifestations. It can affect several different systems, including neurological, musculoskeletal, and dermatological systems. However, one of the most concerning biological systems affected is the cardiac system. Lyme carditis typically presents with varying degrees of atrioventricular (AV) block. Additionally, current literature also endorses atypical manifestations, including but not limited to atrial fibrillation and bundle branch blocks. These atypical manifestations are important as they can be the first presenting symptoms in patients with Lyme disease. Therefore, educating clinicians on various signs, symptoms, and manifestations of Lyme carditis remains paramount in reducing morbidity and mortality. We conducted a literature review using PubMed, MEDLINE, and CINAHL, collecting a total of 13 articles to gather information on atypical manifestations of Lyme carditis. This literature review serves to summarize the current research and studies describing these cardiac manifestations and the cardiac pathophysiology associated with Lyme disease. These findings aim to contribute to the expanding understanding of Lyme carditis, subsequently preventing long-term effects through prompt diagnosis and treatment.
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CONTEXT: Cardiovascular disease (CVD) is the leading cause of death in the United States. As such, an unmet need exists in the primary and secondary prevention of adverse cardiovascular events (CVEs). Specifically, identifying drugs that can reduce the progression of CVD and serious adverse events is much needed. Drugs that work by reducing platelet aggregation, blocking cholesterol formation (3-hydroxy-3-methyl-glutaryl-coenzyme A [HMG-CoA] reductase inhibitors), and/or blocking inflammation pathways (mainly interleukin-1b [IL-1b]) have been linked to preventing adverse CVEs, including acetylsalicylic acid (ASA, aspirin), statins, colchicine, and IL-1 inhibitors (interleukin-1 receptor antagonists). This systematic review aims to provide insight into utilizing these four agents for the primary and/or secondary prevention of CVD. OBJECTIVES: In this systematic review, we opted to review the efficacy of aspirin, statins, colchicine, and IL-1 inhibitors in the primary and secondary prevention of CVE to provide clinical practitioners with evidence-based practice approaches and determine any unmet needs in their utilization. METHODS: Between October 1 and 12, 2021, a search was conducted and completed on five databases: PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science, and Biomedical Reference Collection: Comprehensive. A total of 13 researchers (V.A., A.H., S.B., V.G., D.C., C.C., C.B., C.A., S.K., J.H., A.K., S.F., and S.E.) were involved in the search and screening of the articles. Search terms included "aspirin, statins, colchicine, IL-1 inhibitors, and primary, secondary, myocardial infarction (MI)." Inclusion criteria included clinical study design, English language articles, all genders older than 50 years old, and established patient history of CVD, including MI. In addition, articles were excluded if they were animal models, in vitro studies, pharmacokinetic studies, systematic reviews, literature reviews, and studies exploring therapies other than those listed in the inclusion criteria. First, five individuals independently sorted through abstracts or articles based on the inclusion and exclusion criteria. Then, a team of 13 individuals sorted through full-text articles of selected abstracts based on the same criteria. A separate researcher resolved conflicts between the team. RESULTS: A total of 725 articles were identified from all databases, from which 256 duplicated articles were removed. Thus, a total of 469 articles abstracts were screened, of which 425 articles either did not meet the inclusion criteria or met the exclusion criteria. A total of 42 articles were retrieved and assessed for full-text review, from which 15 articles were retrieved for analysis. CONCLUSIONS: Statins may prevent primary CVEs based on their role in preventing cholesterol formation. Aspirin, canakinumab, and colchicine may be helpful in the secondary prevention of CVEs due to their blocking of various steps in the inflammation pathway leading to CVD. Future research should primarily focus on the use of canakinumab and colchicine in preventing CVD due to the limited number of studies on these drugs.
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Inibidores de Hidroximetilglutaril-CoA Redutases , Infarto do Miocárdio , Feminino , Humanos , Masculino , Estados Unidos , Pessoa de Meia-Idade , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Aspirina/uso terapêutico , Colchicina/uso terapêutico , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/prevenção & controle , Colesterol , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Interleucina-1RESUMO
[This corrects the article DOI: 10.7759/cureus.34860.].
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Osteoarthritis is a degenerative joint disease that is extremely prevalent in society. It affects more than 25% of Americans above the age of 18 years. According to July 2020 publication by the Centers for Disease Control (CDC), osteoarthritis affects approximately 325 million Americans. One of the organs that is most affected by osteoarthritis is the knee. Over the years, we have developed non-surgical treatments, such as physical therapy (PT) and injections, and surgical treatments, such as total knee arthroplasty (TKA) and arthroscopic lavage, for knee osteoarthritis (KOA). If a patient fails with non-surgical options, which are tried first to avoid the risks of surgery, the patient may be considered for knee surgery. This article will investigate the different non-surgical options and TKA as treatment options for KOA based on current literature. The goal of this paper is to be a comprehensive resource for physicians and patients with KOA to make an informed decision. A systematic literature search was conducted using PubMed. The search terms were based on the type of treatments for KOA. To find articles that compared TKA to non-surgical treatments, the terms included "osteoarthritis", "total knee", and "non-surgical treatments," in combination. For other non-surgical treatments such as PT, weight reduction, and injections, a combination of the treatment, "osteoarthritis", and "knee" were included in the search. For the tier 1 process, any randomized controlled trials were included. Any case reports, observational studies, and cross-sectional studies were eliminated from the search. For the tier 2 review process, any articles that did not have relevance to the topic were eliminated after reading the abstracts of the articles. After review of the literature, the data seem to suggest that TKA with 12 weeks of non-surgical treatment improved pain and functionality of the knee more than just 12 weeks of non-surgical treatment when followed up at 12 and 24 months. However, non-surgical treatment before TKA delays the need for surgery. Supervised PT, either in a group or individual format, has been shown to delay TKA in 95% patients in the group that received PT at the end of one year. In addition, weight reduction has been shown as an effective strategy to improve pain and functionality in KOA patients, which decreases the urgency for surgery. Furthermore, platelet-rich plasma (PRP) injections have been shown to have long-term symptomatic relief for KOA compared to hyaluronic acid (HA) and corticosteroid injections. However, HA and corticosteroid injections are beneficial in treating KOA more than receiving no treatment. Physicians often have difficulty deciding whether to pursue conservative or surgical treatment for patients with KOA. The non-surgical treatments explored in this review - PT, injections, and weight reduction - can provide symptomatic relief and, in some cases, delay the need for surgical intervention. However, based on some randomized clinical trials mentioned in the article, patients receiving TKA have more relief, better quality of life, and improved functionality compared to non-surgical therapy. However, a critical review of this important field of debate shows that there are limited randomized controlled studies comparing the effectiveness of TKA and non-surgical treatments for KOA. We believe that this controversial topic needs further clinical investigation.
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Rheumatoid arthritis (RA) is a chronic, progressive autoimmune condition that affects up to 1% of the world population and symmetrically affects the joints leading to joint stiffness and decreased mobility. RA patients present with increased pain and chronic inflammation within their joint spaces, which researchers have linked to poorer sleep patterns, including difficulty falling asleep and non-restorative sleep. As such, identifying mediators of poor sleep quality among RA patients may improve their long-term quality of life. More recently, researchers identified an association between chronic inflammation in RA patients and their circadian rhythm. Altered circadian rhythms negatively impact the hypothalamic-pituitary-adrenal (HPA) axis and lead to altered cortisol release. Cortisol has shown to have a strong anti-inflammatory effect; when dysregulated, it may lead to increased pain experienced in RA patients. This literature review aims to provide insight into how chronic inflammation tied to RA pathophysiology may affect clock genes that are involved in maintaining the circadian rhythm. Specifically, this review focused on four common clock genes found dysregulated in RA patients: circadian locomotor output cycles kaput (CLOCK), brain and muscle ARNT like-1 (BMAL1), period (PER), and cryptochrome (CRY). Of the four clock genes discussed in this review, BMAL1 and PER are the most well-studied of the affected genes. Further knowledge surrounding clock genes and their dysregulated expression in RA may help guide therapy decisions for RA patients. Traditionally, disease-modifying antirheumatic drugs (DMARDs) have been used as first-line therapy for RA patients. Meanwhile, chronotherapy, optimizing drug release in a timed manner, has shown positive results in RA patients as well. Because of the association of altered circadian rhythms with increased symptom severity in RA patients, it seems highly plausible that DMARD therapy with chronotherapy may be an ideal therapeutic regimen for RA.
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Though the concurrence of primary brain tumors and multiple sclerosis (MS) is exceedingly rare, instances have been noted in the literature as early as 1949. Given these observations, researchers have proposed various ideas as to how these malignancies may be linked to MS. Due to insufficient data, none have gained traction or been widely accepted amongst neurologists or neuro-oncologists. What is abundantly clear, however, is the mounting uncertainty faced by clinicians when caring for these individuals. Concerns persist about the potential for disease modifying therapies (DMTs) to initiate or promote tumor growth and progression, and to date, there are no approved treatments capable of mitigating both MS disease activity and tumor growth, let alone established guidelines that clinicians may refer to. Collectively, these gaps in the literature impose limitations to optimizing the care and management of this population. As such, our hope is to stimulate further discussion of this topic and prompt future investigations to explore novel treatment options and advance our understanding of these concurrent disease processes. To this end, the chief objective of this article is to evaluate proposed ideas of how the diseases may be linked, outline emerging therapies for both MS and brain tumors, and describe evidence-based approaches to diagnosing and treating this patient population.
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Neoplasias Encefálicas , Glioma , Esclerose Múltipla , Humanos , Esclerose Múltipla/complicações , Esclerose Múltipla/terapia , Neurologistas , Glioma/complicações , Glioma/terapia , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/terapiaRESUMO
Tobacco use, hypertension, diabetes, and hypercholesterolemia are known risk factors for peripheral artery disease (PAD). However, additional causes of PAD, such as radiation therapy, should be considered for the prevention and diagnosis of this disease. The patient described in this report had 36 radiation therapies directly to the pelvis and bladder area due to bladder cancer. The presence of severe PAD on this patient's right external iliac artery, the same area where he received radiation therapy, raises the question of whether radiation therapy contributed to the development of PAD. In addition, his history of anal intraepithelial neoplasia, obstructive uropathy, and chronic kidney disease further demonstrated that he possibly suffered extensive tissue damage due to radiation to the pelvis. This case report explores the current diagnosis guidelines and treatment options for patients with radiation-induced PAD. Through this case study, we aim to bring awareness to this lesser-known cause of PAD among medical providers and promote research for the prevention and treatment of this disease.
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Diabetes mellitus, a condition in which the body's ability to produce insulin is impaired, and osteoarthritis (OA), a painful degeneration of joint cartilage, are both serious conditions that affect millions of people in the United States (U.S.). Osteoarthritis is a chronic degenerative condition of the joint cartilage, affecting mainly the older population. The purpose of this paper is to find a connection, if any, between diabetes and osteoarthritis and if either condition can predispose an individual to the other. Not only can this review help to explain the co-existence of these two diseases, but it can also be used to look into a cure for patients in the future. After preliminary searches were done on PubMed, results were narrowed using specific keywords and similar risk factors among the two diseases. It was found that these two conditions are actually interrelated due to oxidative stress and pro-inflammatory cytokines. Seeing the high risk of developing one of these conditions and that obesity, one of the biggest risk factors for both diabetes and osteoarthritis, is at an all-time high in this country, a possible connection between the two of these diseases is very prevalent to look into. This information can be used to help correlate not only a better-targeted treatment but also lead to future research into why obesity is one of the biggest risk factors for both conditions.
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Tumor necrosis factor-alpha (TNF-α) inhibitors have been shown to be well tolerated among patients with rheumatoid arthritis, inflammatory bowel disease, and psoriasis. Meanwhile, more recently, clinical practice and research efforts have uncovered increasing cases of psoriatic lesion development tied to initiating treatment with a TNF-α inhibitor. The underlying mechanisms associated with this occurrence have yet to be fully elucidated. A review and analysis of cases of paradoxical psoriasis currently published in the literature is warranted. In addition, exploring possible mechanisms of action and potential treatment options associated with favorable outcomes is much needed. A systematic literature review was performed utilizing PubMed and Google Scholar databases (1992-present), in which 106 cases of paradoxical psoriasis were reviewed. The most common morphology developed was plaque psoriasis vulgaris. There was a female predominance (61.3%), and the most common underlying autoimmune disease was rheumatoid arthritis (45.3%). In addition, the most commonly associated drug with the onset of psoriatic lesions was infliximab (62.3%). Furthermore, the findings suggest that the most well-supported mechanism of action involves the uncontrolled release of interferon-alpha (IFN-α) from plasmacytoid dendritic cells (pDCs) after TNF-α inhibition. While TNF-α inhibitors have been shown to have great benefits to patients with rheumatologic diseases, cases of paradoxical psoriasis demonstrate the importance of close monitoring of patients on TNF-α inhibitors to allow for early recognition, treatment, and potentially change to a different mechanism of action of the medication used to prevent further progression of the inflammatory lesions.
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Cancer is a leading cause of mortality around the world, despite continued advancements in the management of cancer. Recent research efforts have shifted to evaluating the role that modifiable risk factors play in cancer risk and development, as diet and nutrition have been found to play a significant role in the onset and progression of cancer. As a result, there has been an increasing focus on the impact of dietary modifications on preventing the onset, progression, and reoccurrence of cancer. In this systematic review, data were collected on three common diets, the Mediterranean diet (MD), ketogenic diet (KD), and plant-based diet, to gain insight into the application of these three dietary modification approaches for risk prevention and limitation of cancer burden. Initially, 4,397 articles were identified from three databases (Ovid, Web of Science, and CINHAL). After removing studies based on the exclusion criteria, only 23 studies were eligible to be included in the systematic review of which 15 evaluated the MD, four assessed the ketogenic diet, and four evaluated the plant-based diet. Each article was considered for its methods, procedures, and findings. The findings indicate that dietary interventions may effectively reduce the odds of cancer development and the advancement of diagnosed cancers. With the introduction of the MD, KD, and plant-based diets, significant improvements in lowering cancer development, recurrence-free status, and limiting tumor growth were noted across numerous cancer types. Currently, the MD has been extensively studied in the literature, and amongst the widest variety of cancer types. Additional information and evaluation are required on the ketogenic and plant-based diets to fully understand their impact on the cancer burden across a wider subset of cancers. Clinicians should evaluate and recommend nutritional adaptations to their patients to limit the development of specific cancers and as an adjunctive therapy to traditional pharmacological treatment options for patients with diagnosed cancers.
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Systemic lupus erythematosus (SLE) is a complex and chronic autoimmune disease that impacts multiple organ systems and presents with varying symptomatology that makes targeting treatment extremely difficult. The cardiovascular system and more specifically the coronary arteries are heavily affected by SLE causing increased atherosclerosis and subsequently increased acute coronary syndrome (ACS) and increased future cardiac events. ACS is a common occurrence in patients with SLE due to the premature development of atherosclerosis due to the dysregulation of pro-inflammatory cytokines. Calcium scoring has been effectively utilized to identify plaque burden in patients with coronary artery calcification (CAC). Calcium scoring is a score obtained from a computed tomography (CT) image using non-contrast imaging, which provides quantitative information regarding CAC and aids in assessing cardiovascular risk. A calcium score of zero Hounsfeild units can be obtained using CT calcium scoring which indicates no calcium is identified in the coronary arteries and is a strong negative risk predictor for coronary artery disease. Early screening of SLE patients with CT calcium scoring could aid in early detection and treatment subsequently leading to delay of premature coronary atherosclerosis and future cardiac events in this patient population. Multiple studies have used calcium scoring as a method to measure arterial calcification in SLE patients. The Society of Cardiovascular Imaging has now endorsed the idea of obtaining a baseline calcium artery score with a repeat progression scan in 3-5 years. Calcium scoring has also been identified as an effective initial tool for stratification and identification of possible ACS. The various advantages of early calcium scoring signify the further research needed to fully understand and implement the advantages calcium scoring has to offer patients with SLE.