Pathology of breast cancer metastasis and a view of metastasis to the brain.

Despite the advances in diagnosis and management of breast cancer, metastasis has been responsible for the staggering percentage of breast cancer-related death. Mortality threat can be explained mostly by the lack of proper understanding of the diversity of pathological features and underlying mechanism of breast cancer metastasis and effective targeted therapy. Breast cancer stem cells (BCSCs) are the potential source of tumor cells spread to distant organs. BCSCs targeted therapy can suppress the breast cancer progression to metastasis. Spreading of tumor cells to the bone, lung, liver, and brain occurs through a distinct non-random process; called metastasis organotropism. Recently, brain metastasis in breast cancer patients has been detected more frequently, causing a significant clinical burden. BRCA1 and BRCA2 associated breast cancers carry a remarkably higher propensity of CNS metastasis. BRCA1 and BRCA2 associated breast cancers commonly have the propensity to be the triple-negative (TN) and hormone receptors (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative molecular subtypes, respectively. Regardless of molecular subtypes, metastasis is most commonly evident at the bone. Heterogeneity is a critical pathological feature, leads to therapeutic resistance. BCSCs, biomarkers expression patterns, and mutations contribute to heterogeneity. In this paper, we discuss crucial pathological features of breast cancer metastasis, emphasizing metastasis organotropism and heterogeneity; and mechanisms of breast cancer metastasis, highlighting the pathways of metastasis to the brain. We consider that this paper reinforces future research areas and benefits the general readers, physicians, and researchers to identify potential areas to develop targeted therapies.

An Update on Treatment Options for Methicillin-Resistant Staphylococcus aureus (MRSA) Bacteremia: A Systematic Review.

Since the last century, methicillin-resistant Staphylococcus aureus (MRSA) bacteremia has become a major global and public health concern not only in terms of morbidity and mortality but also the duration of hospital stay, healthcare cost, and antimicrobial choices. Especially alarming is the growing antimicrobial resistance due to their misuse and overuse, which has led the world to be exhausted of its effective antibiotic resources. In this review article, we sought to figure out the most efficacious antimicrobial agents to treat MRSA-related bloodstream infections. We compared the data from reviewing reports from 2017 to 2022 and summarized their comparative efficacy and cost-effectiveness. Although we focused on vancomycin and daptomycin, which are the current Infectious Disease Society Of America (IDSA)-recommended antibiotics for MRSA bacteremia treatment, a deep dive into the newer agents revealed better efficacy and treatment outcome in the combination of ceftaroline (ß-lactam) with daptomycin compared to traditional standard monotherapy (vancomycin/daptomycin monotherapy). Also, the IDSA recommended high-dose daptomycin (8-10 mg/kg) therapy for MRSA bacteremia treatment to be more effective in cases with vancomycin-reduced susceptibility. Moreover, we did not find any trial or study describing the use of ceftaroline as a monotherapy to compare its efficacy in MRSA bacteremia with the current standard therapy. The upshot is that we need more large-scale clinical trials exploring in-depth effectiveness and adverse effects to decide on newer agents like ß-lactams to use as routine therapy for MRSA bacteremia.

A Multidisciplinary Approach and Current Perspective of Nonalcoholic Fatty Liver Disease: A Systematic Review.

In recent times, nonalcoholic fatty liver disease (NAFLD) has been considered one of the major causes of liver disease across the world. NAFLD is defined as the deposition of triglycerides in the liver and is associated with obesity and metabolic syndrome. Hyperinsulinemia, insulin resistance (IR), fatty liver, hepatocyte injury, unbalanced proinflammatory cytokines, mitochondrial dysfunction, oxidative stress, liver inflammation, and fibrosis are the main pathogenesis in NAFLD. Recent studies suggest that the action of intestinal microbiota through chronic inflammation, increased intestinal permeability, and energy uptake plays a vital role in NAFLD. Moreover, polycystic ovarian syndrome also causes NAFLD development through IR. Age, gender, race, ethnicity, sleep, diet, sedentary lifestyle, and genetic and epigenetic pathways are some contributing factors of NAFLD that can exacerbate the risk of liver cirrhosis and hepatocellular carcinoma (HCC) and eventually lead to death. NAFLD has various presentations, including fatigue, unexplained weight loss, bloating, upper abdominal pain, decreased appetite, headache, anxiety, poor sleep, increased thirst, palpitation, and a feeling of warmth. Some studies have shown that NAFLD with severe coronavirus disease 2019 (COVID-19) has poor outcomes. The gold standard for NAFLD diagnosis is liver biopsy. Other diagnostic tools are imaging tests, serum biomarkers, microbiota markers, and tests for extrahepatic complications. There are no specific treatments for NAFLD. Therefore, the main concern for NAFLD is treating the comorbid conditions such as anti-diabetic agents for type 2 diabetes mellitus, statins to reduce HCC progression, antioxidants to prevent hepatocellular damage, and bariatric surgery for patients with a BMI of >40 kg/m2 and >35 kg/m2 with comorbidities. Lifestyle and dietary changes are considered preventive strategies against NAFLD advancement. Inadequate treatment of NAFLD further leads to cardiac consequences, sleep apnea, chronic kidney disease, and inflammatory bowel disease. In this systematic review, we have briefly discussed the risk factors, pathogenesis, clinical features, and numerous consequences of NAFLD. We have also reviewed various guidelines for NAFLD diagnosis along with existing therapeutic strategies for the management and prevention of the disease.

Exacerbation of Pre-existing Neurological Symptoms With COVID-19 in Patients With Chronic Neurological Diseases: An Updated Systematic Review.

The neurotropism of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can potentially explain the worsening of symptoms in patients with a history of neurological conditions such as stroke, Parkinson's disease, Alzheimer's, and epilepsy. Several studies have reported that these pre-existing conditions may worsen with a higher frequency of flare-ups, thus resulting in a more significant risk of patient mortality. In this review, we sought to provide an overview of the relationship between pre-existing neurological disorders and COVID-19, focusing on whether the initial infection directly influenced the severity of symptoms. We systematically searched the electronic database PubMed (MEDLINE) and used specific keywords related to our aims from January 2020 to July 2022. All articles published on COVID-19 with keywords pertaining to pre-existing neurological diseases were retrieved and subsequently analyzed. After independent review, the data from 107 articles were selected and evaluated. After analyzing the data from selected articles reviewing the effect of COVID-19 on neurological conditions, we have documented the relationship between said pre-existing neurological diseases, showing an increased risk of hospitalization, admission length, worsening of symptoms, and even mortality in COVID-19 patients.

Osteoporosis, an Inevitable Circumstance of Chronic Kidney Disease: A Systematic Review.

Nowadays, chronic kidney disease (CKD) and osteoporosis have become crucial health-related issues globally. CKD-induced osteoporosis is a systemic disease characterized by the disruption of mineral, hormone, and vitamin homeostasis that elevates the likelihood of fracture. Here, we review recent studies on the association of CKD and osteoporosis. In particular, we focus on the pathogenesis of CKD-associated osteoporosis, including the homeostasis and pathways of several components such as parathyroid hormone, calcium, phosphate, vitamin D, fibroblast growth factor, and klotho, as well as abnormal bone mineralization, remodeling, and turnover. In addition, we explore the diagnostic tools and possible therapeutic approaches for the management and prevention of CKD-associated osteoporosis. Patients with CKD show higher osteoporosis prevalence, greater fracture rate, increased morbidity and mortality, and an elevated occurrence of hip fracture. We also rule out that increased severity of CKD is related to a more severe condition of osteoporosis. Furthermore, supplements such as calcium and vitamin D as well as lifestyle modifications such as exercise and cessation of smoking and alcohol help in fracture prevention. However, new approaches and advancements in treatment are needed to reduce the fracture risk in patients with CKD. Therefore, further collaborative multidisciplinary research is needed in this regard.

Mediterranean Diet and Physical Activity: Two Imperative Components in Breast Cancer Prevention.

Despite tremendous advances in medicine over the past few decades and significantly improved understanding of the symptomology and contributors to breast cancer (BC) incidence, BC rates continue to rise worldwide, with BC being a leading cause of cancer-related death among women. To reduce BC incidence, it is necessary to focus on promoting prevention strategies through a population-based approach of lowering exposure to modifiable risk factors in addition to the application of newer drug interventions (chemoprevention) for prevention in high-risk populations. Currently, available data suggest that lifestyle modifications through a healthy diet and increased physical activity (PA) play a crucial role in BC prevention; specifically, there is growing evidence to indicate that the Mediterranean diet (MeD) lowers cancer risk. This review summarizes the potential role of the MeD and PA in reducing BC risk, with an additional focus on microbial modulation in BC prevention, based on the current evidence obtained from PubMed. After reviewing the immunomodulatory and anticarcinogenic effects of both the MeD and PA, we conclude that further evaluation and proper implementation of both interventions can significantly reduce the risk of BC and associated mortality in the general population.

Identifying the Neurogenetic Framework of Crohn's Disease Through Investigative Analysis of the Nucleotide-binding Oligomerization Domain-containing Protein 2 Gene Mutation.

Among several inflammatory bowel diseases, Crohn's disease is associated with inflammation that may take place in any region of the gastrointestinal tract. The inflammatory process is most commonly associated with the ileum, often spreading deep into the bowel tissues, extending into multiple forms, such as strictures and penetrations. Currently, Crohn's disease has no known cure. Various medical and surgical procedures are used to manage the condition. The underlying mechanisms of the disease are yet to be identified, with recent studies suggesting the influence of genetics, environmental factors, and the possible activity of pathogens. Newer studies also offer strong evidence that suggests a relationship between Crohn's disease and the nucleotide-binding oligomerization domain-containing protein 2 (NOD2) gene, also known as inflammatory bowel disease protein 1 (IBD1) or caspase recruitment domain-containing protein 15 (CARD15). NOD2 is responsible for the mechanism in which the immune system identifies foreign microorganisms through the sensing of pathogen-associated molecular patterns in microorganisms. NOD2 can detect intracellular muramyl dipeptide (MDP) in the bacterial wall, thereby causing an inflammatory response. Three major mutations associated with the NOD2 gene are known to have an influence on Crohn's disease (SNP8, SNP12, and SNP13). This article will discuss a number of studies to identify whether there is a relationship between Crohn's disease and the NOD2 gene.

A Case of Granulomatosis with Polyangiitis (Wegener's Granulomatosis) Presenting with Rapidly Progressive Glomerulonephritis.

Granulomatosis with polyangiitis (GPA, Wegener's granulomatosis) presenting as rapidly progressive glomerulonephritis is not uncommon. The recognition of multisystem disease involving joints, kidney, and lung is critical for diagnosing Wegener's vasculitis. Here, we report a case study of a 52-year-old Bangladeshi man presented with a history of progressively worsening fever, recurrent cough, and hemoptysis. He developed renal failure within a month which was successfully treated with high-dose steroids, cyclophosphamide, and trimethoprim-sulfamethoxazole (TMP-SMX). Rapidly progressive glomerulonephritis can be a fulminant manifestation of GPA, in which case an immediate and aggressive treatment with pulse steroids, high-dose cyclophosphamide and TMP-SMX can be lifesaving.

The Neurocognitive Effects of Ghrelin-induced Signaling on the Hippocampus: A Promising Approach to Alzheimer's Disease.

The communication between the gastrointestinal tract and the central nervous system (CNS) allows for certain peptide hormones to influence neurocognitive function. Ghrelin, also known as the 'hunger hormone,' has the unique ability to enter the CNS and interact with the growth hormone secretagogue receptor (GHS-R) within the hippocampus. Upon interaction with ghrelin, a conformational change in the receptor causes an increase in transcription factors to foster a wide array of physiologic changes in response to caloric deprivation. With the GHS-R in a relatively high concentration within the hippocampus, ghrelin can promote memory, spatial, learning, and behavioral effects. In fact, ghrelin appears to also have a neuroprotective and neuromodulatory response once active within the hippocampal dentate gyrus. Through the GHS-R, higher levels of ghrelin may alter cognitive circuitry and offer a possible link to the treatment of some pathologies implicated in neurological dysfunction. Alzheimer's disease (AD) is already becoming a significant target for ghrelin neuroreceptor therapy. In such experimental models, ghrelin has been shown to combat this degenerative process by eliciting an ameliorative and regenerative response. Although trials and research are still ongoing, further studies are indicated as early research into this adjuvant therapy is promising. The research team explored the effects of ghrelin by reviewing the downstream signaling modifications of ghrelin's interaction with a specific CNS receptor, the GHS-R. Although the GHS-R is found in multiple locations within the CNS, the team investigated the role of the GHS-R within the hippocampus to focus solely on the neurocognitive implications of ghrelin. The team noted which signaling pathways in particular that ghrelin initiated and used this approach to determine whether ghrelin may have any therapeutic benefits. The team explored the possible therapeutic indications of ghrelin by looking at studies conducted with a specific neurodegenerative disease known to target the hippocampus.