Evolving Indications of Transcatheter Aortic Valve Replacement Compared to Surgical Valve Replacement: A Review of the Current Literature.

Patients with severe symptomatic aortic stenosis (AS) are categorized into high risk, intermediate risk, and low risk. The identification of risk status is done using the Society of Thoracic Surgeons mortality score. Various factors are considered such as clinical symptoms, ejection fraction, age, left ventricle measurements, severity of AS, associated comorbid factors, and any other associated cardiac diseases. Surgery is still a standard practice in many countries. However, it has its own complications, especially in high-risk patients. Transcatheter intervention is getting precipitous recognition as an alternative mode of treatment in selected cases to mitigate complication rates and improve quality of life. In this article, transcatheter aortic valve replacement and surgical aortic valve replacement are compared in patients with different surgical risks. The impact of the cost of the procedure and quality of life are of paramount importance in choosing the type of intervention. Structural valve degeneration is an independent risk factor affecting patient outcomes. Modifications in valve designs are being constantly implemented as well. The standard analytical methods are in accordance with randomized clinical trials to determine the efficacy and outcome of procedures. Primary and secondary endpoints were considered to evaluate the data. The results were tabulated to derive statistical significance of the studies. In high-risk surgical patients, transcatheter intervention has been proven as the procedure of choice for valve replacement. However, intermediate-risk and low-risk categories need further studies.

Food Allergy Prevention: Early Versus Late Introduction of Food Allergens in Children.

The emergence of food allergies in children is crucial for various medical fields seeking a viable strategy for allergy prevention. The most well-recognized approach adopted by numerous health care and government institutions hinges on the delay in the introduction of food allergens, which supposedly protects infants from sensitization and decreases the possibility of allergy development. However, recent experimental findings indicate that the benefits of this approach might be overestimated, as early exposure to allergenic foods has been shown to yield more advantageous outcomes. Multiple investigations on the causes of allergic diseases report that avoiding food allergies might be related to early consumption of these allergens. Alternatively, delaying the contact with allergenic nourishments, explored in contemporary research, has been proven to result in a higher prevalence of allergies among children, originating such conditions as atopic diseases and extreme sensitization to foods. The current paper compares the two prominent strategies of allergenic food introduction, gathering the most pertinent modern evidence to distinguish whether exposure to food allergens should be delayed or advanced.

Role of Immunotherapy in the Treatment of Triple-Negative Breast Cancer: A Literature Review.

Numerous malignancies, including metastatic triple-negative breast cancer (TNBC), which has long been associated with a poor prognosis, have been transformed by the widespread use of immunotherapy. Immune checkpoint inhibitors (ICIs) that target and block programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) have demonstrated encouraging outcomes in the treatment of patients with metastatic TNBC. The PD-1 inhibitor pembrolizumab is the first-line treatment of metastatic PD-L1+ TNBC in combination with chemotherapy, and the PD-L1 inhibitor atezolizumab has also shown clinical activity. The median progression-free survival for pembrolizumab or atezolizumab combined with chemotherapy increased by 4.1 months and 2.5 months, respectively, with the addition of immunotherapy. Despite this progress, there is still more to be desired. The addition of immunotherapy to chemotherapy improved the pathological complete response (PCR) rate compared to chemotherapy with placebo in landmark phase III trials in the early-stage neoadjuvant context, whereas others reported no meaningful improvement in PCR. There are various ongoing trials that show that more research and studies are needed for components in the TNBC microenvironment and to further explore its importance in the treatment of TNBC.

Diagnosing Torsades De Pointes Based on Correlation to QT Interval: A Systematic Review.

Torsades de Pointes (TdP) is a rare form of tachyarrhythmia which can potentially be fatal due to its tendency to degenerate into ventricular fibrillation. It is described as a polymorphic ventricular tachycardia characterized by twisting of the QRS complexes around the electrocardiogram (ECG) baseline in patients with a prolonged QT interval. Prolonged QT interval is known as long QT syndrome. Torsades de Poccurs most commonly in patients with an extended QT interval duration, and even though monitoring an ECG can assist in its prevention, there is no defined duration of a QT interval that can lead to an increased risk of Torsades de Pointes. So, it is hard to determine what QT interval constitutes enough risk for Torsades de Pointes to require intervention. The QT interval duration also depends on other factors, namely heart rate (HR) and other factors such as drugs, congenital diseases, and a combination of both. In this study, we considered various causes of QT prolongation but mainly focused on congenital diseases, drugs, or perioperative risk of QT prolongation and the correlation with the risk of impending TdP. By following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and researching studies on various databases, namely PubMed, Science Direct, Medline, and CiNii we were able to find various systematic reviews and articles showing the association between prolonged QT interval and its degeneration into TdP. This review encourages further research into this topic to understand the implications of QT prolongation and how it can help save the lives of patients with known long QT syndrome, or those on QT prolonging drugs with simple ECG monitoring and treatment for the respective cause.

Influence of Subclinical Hypothyroidism on Women With Polycystic Ovary Syndrome: A Literature Review.

Subclinical hypothyroidism (SCH) is a commonly encountered condition in women with polycystic ovary syndrome (PCOS). Nevertheless, it is unclear whether SCH has any potential impact on the metabolic and reproductive profiles of women with PCOS. Hence, this literature review explores and establishes the link between these two conditions. In women with PCOS, SCH was found to aggravate insulin resistance and dyslipidemia. It was also linked to hormonal imbalances leading to higher infertility rates among the PCOS-SCH group. Therefore, women with PCOS must be screened for thyroid function frequently and managed accordingly.

Tumor Necrosis Factor-Alpha Inhibitors and Cardiovascular Risk in Rheumatoid Arthritis: A Systematic Review.

Rheumatoid arthritis (RA) is an autoimmune disease that, if untreated or poorly controlled, can cause significant morbidity in terms of loss of physical function and higher mortality due to higher cardiovascular risk. The standard of care for this disease is the use of disease-modifying antirheumatic drugs (DMARDs). However, patients unable to reach low disease activity or remission and patients unable to tolerate conventional DMARDs will be switched to biologic therapy, a subset of which includes anti-tumor necrosis factor-alpha inhibitors. Since tumor necrosis factor-alpha inhibitors (TNFi) inhibit the inflammatory cascade, they also play an essential role in dampening the progression of atherosclerosis and altering the risk of cardiovascular outcomes in RA. In this study, we assessed the risk of cardiovascular diseases, namely, congestive heart failure, nonfatal myocardial infarction, cerebrovascular disease, and coronary artery disease. We carried out the analysis by following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and conducted a literature search utilizing the following databases: PubMed, Science Direct, and Cochrane Library. Using the search strategy, we found a total of 19 articles that fit the inclusion and exclusion criteria, in addition to passing the risk of bias assessment. This is composed of three systematic reviews with meta-analyses, three randomized control studies, four narrative reviews, and nine cohort studies. In this systematic review, it was found that treatment with TNFi causes a corresponding reduction in the risk of cardiovascular events. This review encourages further dissection into the inner workings of TNFi in reducing the risk of cardiovascular disease among patients with RA.

Efficacy of Brentuximab Vedotin and Nivolumab in Refractory or Relapsed Hodgkin Lymphoma: A Systematic Review.

The central dilemma in treating patients with refractory or relapsed classical Hodgkin lymphoma (RRHL) is the developed resistance to chemotherapy. In recent years, significant advances have been made with the introduction of targeted immunotherapy such as brentuximab vedotin (BV) and nivolumab (NV). As monotherapy, BV and NV have demonstrated high response rates but with an opportunity for disease progression. In other studies, BV or NV is given in combination with chemotherapy as a bridge to hematopoietic stem cell transplantation for curative therapy. This review will investigate the effect of BV and NV as single agents, in combination with each other, or given concurrently with chemotherapy on the response and survival rate of patients with RRHL.

Lung Ultrasonography Beyond the Diagnosis of Pediatrics Pneumonia.

Pneumonia is a prevalent disease with considerable morbidity and mortality among the pediatric population. Early diagnosis and swift commencement of the correct treatment are vital for a favorable clinical outcome. Along with history-taking and clinical examination, imaging modalities commonly used, lung ultrasound provides a bedside, less invasive, radiation-free alternative to diagnose pneumonia when compared with other images such as chest x-ray (CXR) and computed tomography (CT) scan. It is therefore of the utmost magnitude to inspect the evidence of its accuracy and reliability in the diagnosis of this condition. The goal of this study is to look into the available data supporting the use of lung ultrasound in the diagnosis of juvenile pneumonia, its relevance in distinguishing between viral and bacterial diseases, and its superiority as compared to other diagnostic methods. As mentioned, early detection and differentiation of the type of pneumonia can reduce unnecessary antibiotic prescriptions and provide patients with a better prognosis, as well as the ability to predict the course of the disease and the need for advanced care or the development of complications. An extensive literature search of two popular online medical websites (PubMed and Embase) was conducted in this review, concentrating on studies that examined the role of lung ultrasound in the diagnosis of pediatric pneumonia published in the last five years. Only studies published in the English language were included in this review. With high sensitivity and specificity, lung ultrasound appeared to be a promising tool not only for pediatric pneumonia diagnosis, but also for treatment guidance and disease follow-up, especially when combined with clinical presentation and laboratory findings.

Fecal Microbiota Transplant in Recurrent Clostridium Difficile Infections: A Systematic Review.

Fecal Microbiota Transplantation (FMT) is the process of transferring the fecal microbiome from a healthy donor to an individual with repeated multiple episodes of Clostridium difficile infection. It is also known as stool transplant. Fecal microbiota transplant is effective and safe in various studies, the approval from the Food and Drug Administration (FDA) remains pending. The main objective of this systemic review is to evaluate the efficacy and safety of stool transplant in studies with only treatment groups (FMT) and studies with treatment (FMT) and antibiotic (AB) groups and previous studies. Online databases PubMed, PubMed Central, Science Direct, Google Scholar, and Embase were searched for relevant articles in the last five years (2016 to 2021) using automation tools. Following the removal of duplicates, screening of eligibility criteria, titles/abstracts, and quality appraisal were done by two authors independently. In total, seven observational studies are in this review article. Out of the seven observational studies, five are retrospective and two prospective. Two of the five retrospective and one of two prospective studies have a control group. In both the prospective studies and one retrospective study, FMT efficacy of (68% to 93%) was demonstrated in the elderly population despite high index comorbidities. In the younger individuals with inflammatory bowel disease, and efficacy of 90% or above was found. The most common side effects were minor such as fever, abdominal pain, bloating, and flatulence. In one study, two cases of aspiration events occurred attributed to the gastroscopy route of donor feces delivery. There was no statistical significance in the incidence of diseases such as (allergies, autoimmune diseases, cancer, inflammatory bowel diseases, and neurological diseases like dementia and migraine).  Fecal microbiota transplantation has shown to be effective and safe in recurrent Clostridium difficile infections. Since very few pragmatic studies have demonstrated its efficacy and safety, their application is not well established. Robust studies, both observation and experiment, are required in the future to well-establish its effectiveness, safety in the treatment of recurrent Clostridium difficile infection.

An Outlook on the Etiopathogenesis of Pulmonary Hypertension in HIV.

Although overall survival rates of patients infected with human immunodeficiency virus (HIV) have been significantly improved by antiretroviral therapy (ART), chronic comorbidities associated with HIV result in a worsening quality of life. Pulmonary arterial hypertension (PAH) is the most prevalent comorbidity associated with HIV infection. Despite low viremia and a non-replicative state maintained by ART, few people develop PAH. Previous data from animal models and human pulmonary microvascular endothelial cells (HPMVECs) suggests a constellation of events occurring during the propagation of HIV-associated PAH (HIV-PAH). However, these studies have not successfully isolated HIV virions, HIV-DNA, protein 24 antigen (p24), or HIV-RNA from the pulmonary endothelial cells (ECs). It provides an insight into an ongoing inflammatory process that could be attributed to viral proteins. Several studies have demonstrated the role of viral proteins on vascular remodeling. A composite of chronic inflammatory changes mediated by cytokines and growth factors along with several inciting risk factors such as Hepatitis C virus (HCV) co-infection, genetic factors, male predominance, illegal drug usage, and duration of HIV infection have led to molecular changes that result in an initial phase of apoptosis followed by the formation of apoptotic resistant hyperproliferative ECs with altered phenotype. This study aims to identify the risk factors and mechanisms behind HIV-PAH pathobiology at the host-pathogen interface at the intracellular level.

The Role of Metformin in Ovarian Cancer: Does Metformin Increase Survival in Ovarian Neoplasm?

The role of metformin in ovarian cancer (OC) remains a topic of research and open discussion. Because OC has a high mortality rate for various reasons, finding a solution is vital. Although metformin has demonstrated a high level of evidence in preventing and increasing survival in other cancers, its role in OC is still not proven. This review highlights the function of metformin as an antineoplastic agent in OC and its effect on overall survival, progress-free survival, and recurrence-free survival. We conducted a literature search in the PubMed database using the medical subject heading keywords, ovarian neoplasm and metformin. The search yielded 94 articles, of which 86 remained after including only English language articles. Finally, 50 articles published between 1997 and 2020 were reviewed. We recommend more randomized controlled trials in the future to determine the safety and efficacy of metformin in OC.

Anti-N-Methyl-D-Aspartate Receptor Encephalitis: A Detailed Review of the Different Psychiatric Presentations and Red Flags to Look for in Suspected Cases.

Anti-N-methyl-D-aspartate receptor encephalitis is a rare autoimmune disorder that involves N-methyl-D-aspartate (NMDA) receptors. It is the most common autoimmune encephalitis, and early detection and treatment are crucial for morbidity-free recovery. Distinguishing this disorder from a primary psychiatric illness is quite challenging as this disorder classically presents with psychiatric manifestations that often resemble schizophrenic psychosis. Therefore, this review intended to scope the psychiatric manifestations this disorder could present with and dissect how they differ from primary psychiatric disorders. A PubMed database search was done. The results yielded were analyzed; eventually, 50 papers were used to review the different signs and symptoms the disease can present with, including common and rare disease presentations. Diagnostic challenges and helpful clinical clues to recognize the disorder were reviewed as well.

Contrast-Enhanced Ultrasound as a Main Radiological Diagnostic Method for Primary Liver Neoplasms and Hemangiomas.

Contrast-enhanced ultrasound (CEUS) is a relatively new approach for the definitive diagnosis of focal liver lesions (FLL). The essential advantages of CEUS are affordability, absence of radiation, and negligible nephrotoxicity-making this diagnostic approach more preferable. This review includes data from 39 different research studies published during the last 10 years, selected through the MeSH strategy in PubMed. We conclude that CEUS is a promising approach for diagnosing primary liver neoplasms and it is an excellent radiological approach for children and pregnant women because of the absence of radiation and nephrotoxicity. Studies showed that CEUS is a very good approach for the differentiation of a variety of hemangiomas and for a detailed description of those findings. Therefore, CEUS is an important and progressive method for the diagnosis of liver neoplasms. The regular use of CEUS will facilitate the diagnosis of primary liver lesions.

Mechanisms and Potential Treatment Options of Heart Failure in Patients With Multiple Myeloma.

Multiple myeloma is a pathology of plasma cells, with one of the most common side effects of its treatment is heart failure. In addition, cardiac amyloidosis could cause heart failure by itself. Even though mechanisms of cardiac amyloidosis are known, and they involve lysosomal dysfunction, reactive oxygen species (ROS) accumulation, and infiltrative effect by fibrils, there is no specific agent that could protect from these effects. While the molecular mechanism of doxorubicin cardiotoxicity via topoisomerase II ß is established, the only FDA-approved agent for treatment is dexrazoxane. Liposomal doxorubicin can potentially improve response and decrease the development of heart failure due to microscopic liposomes that can accumulate and penetrate only tumor vasculature. Supplements that enhance mitochondrial biogenesis are also shown to improve doxorubicin-induced cardiotoxicity. Other agents, such as JR-311, ICRF-193, and ursolic acid, could potentially become new treatment options. Proteasome inhibitors, novel agents, have significantly improved survival rates among multiple myeloma patients. They act on a proteasome system that is highly active in cardiomyocytes and activates various molecular cascades in malignant cells, as well as in the heart, through nuclear factor kappa B (NF-kB), endoplasmic reticulum (ER), calcineurin-nuclear factor of activated T-cells (NFAT), and adenosine monophosphate-activated protein kinase (AMPKa)/autophagy pathways. Metformin, apremilast, and rutin have shown positive results in animal studies and may become a promising therapy as cardioprotective agents. This article aims to highlight the main molecular mechanisms of heart failure among patients with multiple myeloma and potential treatment options to facilitate the development and research of new preventive strategies. Hence, this will have a positive impact on life expectancy in patients with multiple myeloma.

Risk Assessment Using the Association Between Renin-Angiotensin Genes Polymorphisms and Coronary Artery Disease.

Coronary artery disease (CAD) is a multifactorial disease that involves genetic and environmental interaction. In addition to the well-known CAD risk factors, such as diabetes mellitus, hypertension, hyperlipidemia, and atherosclerosis, it has a genetic component that predisposes to its occurrence even in young people. One of the most commonly studied genes that increase the susceptibility to CAD is renin-angiotensin system (RAS) genes polymorphisms mainly angiotensin-converting enzyme gene (ACE) polymorphisms, angiotensinogen polymorphisms, angiotensin- II type 1 receptor gene polymorphisms, and many other genes. These genetic polymorphisms have a direct association with CAD development or indirect association through causing atherosclerosis and hypertension which, in turn, are complicated by CAD later on. The difference between genetic mutations and polymorphisms lies in the frequency of the abnormal genotype. If the frequency is 1% and more in the general population, it is called polymorphism and if it is less than 1%, then it is called a mutation. According to our findings, after thorough searching, which support the association of RAS genes polymorphisms with premature CAD, hypertension, hypertrophic cardiomyopathy, and atherosclerosis, we recommend additional studies in the form of clinical trials and meta-analyses aiming to create a specific diagnostic tool for CAD risk assessment and discovering the high-risk people as early as possible. Targeted gene therapy, being the future of medicine, needs to be taken into researchers' consideration. It can have promising results in these cases.

Can Big Data and Machine Learning Improve Our Understanding of Acute Respiratory Distress Syndrome?

Acute respiratory distress syndrome (ARDS) accounts for 10% of all diagnoses in the Intensive Care Unit, and about 40% of the patients succumb to the disease. Clinical methods alone can result in the under-recognition of this heterogeneous syndrome. The purpose of this study is to evaluate the role that big data and machine learning (ML) have played in understanding the heterogeneity of the disease and the development of various prediction algorithms. Most of the work in the field of ML in ARDS has been in the development of prediction models that have comparable efficacies to that of traditional models. Prediction algorithms have been useful in identifying new variables that may be important to consider in the future, supplementing the unknown information with the help of available noninvasive parameters, as well as predicting mortality. Phenotype identification using an unsupervised ML algorithm has been pivotal in classifying the heterogeneous population into more homogenous classes. Big data generated from ventilators in the form of ventilator waveform analysis and images in the form of radiomics have also been leveraged for the identification of the syndrome and can be incorporated into a clinical decision support system. Although the results are promising, lack of generalizability, "black box" nature of algorithms and concerns about "alarm fatigue" should be addressed for more mainstream adoption of these models.

Association Between Myasthenia Gravis and Systemic Lupus Erythematosus as a Comorbid State.

Systemic lupus erythematosus (SLE) and myasthenia gravis (MG) are autoimmune states which have presentational similitude. Both conditions test serologically positive for anti-nuclear antibodies and require exceptional differential diagnostic acumen to segregate one from the other. The hypothesized factors provoking these diseases may be immunological, genetic, hormonal, or environmental and can be better understood by large-scale controlled epidemiological studies. Biochemical factors such as variation in CXC (an α chemokine subfamily), CXCL13, and granulocyte-macrophage colony-stimulating factor levels are assumed to play a pivotal role in the pathogenesis of SLE and MG; however, further studies are required to understand their exact mechanism and effect on the underlying autoimmune diseases. Following this, another precipitating factor for this overlap is believed to be thymectomy which is performed to eliminate MG symptoms. Although thymectomy is the effective treatment modality in MG patients, other findings and data support the view that this procedure may lead to the development of other autoimmune states such as SLE. It is evident from previously published data and case reports that patients with one autoimmune disease who underwent thymectomy contracted SLE and became more susceptible to other autoimmune diseases compared to the general population. Post-thymectomy follow-up of patients provides us with mechanistic clues for understanding the development of SLE-MG overlap; hence, in MG patients who have undergone thymectomy, any clinical and immune serological SLE suspicion should be carefully evaluated.

Sarcoidosis: Various Presentations, Coexisting Diseases and Malignancies.

Sarcoidosis is a rare, chronic inflammatory disease with a characteristic non-caseating granuloma formation. It affects women more than men. The lung is the most commonly affected organ, however, extrapulmonary involvement is also seen. Sarcoidosis can affect any organ or tissue and can also involve multiple organs simultaneously. As a disease, it shares clinical symptoms with a variety of autoimmune, non-autoimmune disorders and malignancies. Not only it mimics clinically, but it also coexists with these diseases, posing a significant diagnostic challenge. During this literature review, we obtained data from the previously published PubMed articles within the last five years and reviewed the possible etiological association and clinical coexistence between sarcoidosis and other diseases/malignancies. We aimed to determine the common clinical manifestations, various complex presentations of sarcoidosis and pathophysiological considerations for the association, and to emphasize the link with other diseases, particularly thyroid disorders/malignancies. Physicians should be aware of these associated diseases and should always make a clinical suspicion when confronting a sarcoidosis patient. Thus, a comprehensive diagnostic evaluation for these associated conditions ought to be done in sarcoidosis patients to avoid any delay in the curative treatment for these coexisting diseases and to prevent substandard outcomes.

Kikuchi-Fujimoto Disease: A Rare Cause of Cervical Lymphadenopathy.

Kikuchi-Fujimoto disease (KFD) is a rare benign disease, clinically characterized by fever and tender cervical lymphadenopathy affecting the posterior cervical lymph nodes. This disease is usually accompanied by night sweats, rashes, and headaches. It generally affects young individuals, especially females, of Oriental-Asian origin. The etiology of KFD remains uncertain, but associations have been noted with viral diseases including Epstein-Barr virus (EBV), herpes simplex virus (HSV), and varicella-zoster virus (VZV), as well as autoimmune disorders including systemic lupus erythematosus (SLE) and Sjogren's syndrome. This review points out the etiology of KFD with cervical lymphadenopathy alongside its clinical presentation, histological highlights, lab investigations, complications, and treatment. Accurate diagnosis of this disease depends on lymph node excisional biopsy. Three histological patterns of KFD are recognized: proliferative, necrotizing, and xanthomatous. Distinction from lymphadenopathy-associated alternate disorders (e.g., SLE, malignancy, tuberculosis, or another infectious lymphadenitis) is essential to ensure appropriate therapy. This self-limited condition entails nonsteroidal anti-inflammatory drugs (NSAIDs) for pain relief with consideration of corticosteroids and hydroxychloroquine in severe cases.

Role of Rho-Associated Protein Kinase Inhibition As Therapeutic Strategy for Parkinson's Disease: Dopaminergic Survival and Enhanced Mitophagy.

The GTP-binding protein, Rho, plays a significant role in the cellular pathology of Parkinson's disease. The downstream effector of Rho, Rho-associated kinase (ROCK), performs several functions, including microglial inflammatory response and enhanced Parkin-mediated mitophagy. Its inhibition shows neuroprotective effects in carried studies. Parkinson's disease pathology also rests on incomplete removal of damaged mitochondria, leading to neuronal impairment. ROCK has different isoforms, inhibition of which have been shown to decrease the adverse changes in microglia. There has also been evidence of a decreased release of inflammatory cytokines and a reduction in degradation of dopaminergic neurons on the addition of ROCK inhibitors. Additionally, ROCK inhibitors have recently been shown to increase the activity of hexokinase 2 (HK2), relocating it to mitochondria, and therefore leading to upregulated mitochondrial targeting. Understanding the cellular basis of ROCK activity and its inhibition may help us advance in creating new strategies for the treatment of Parkinson's disease.