Probable Enoxaparin-Induced Liver Injury in a Young Patient: A Case Report of a Diagnostic Challenge.

Low molecular weight heparin (LMWH) is associated with elevated liver enzyme levels in a small percentage of patients. Elevations more than five times the upper limit of normal are uncommon and have been noted to primarily occur in patients receiving higher doses. The literature reports mild, primarily asymptomatic cases, with adverse effects at higher therapeutic doses. We report the case of a 27-year-old woman who developed drug-induced liver injury (DILI) while receiving enoxaparin during admission for a loculated pleural effusion secondary to pulmonary tuberculosis. The Roussel Uclaf Causality Assessment Method (RUCAM) score delineated enoxaparin as the likely cause.

Supraventricular Tachycardia in Pregnancy: Gestational and Labor Differences in Treatment.

Supraventricular tachycardia (SVT) is a tachyarrhythmia characterized by a heart rate above 120 beats per minute (BPM). Patients with SVT exhibit the following symptoms: palpitations, shortness of breath, chest pain, hemodynamic instability, or possibly asymptomatic. The increase in cardiac output and the increase in resting heart rate during pregnancy predispose pregnant women to SVT. The management of SVT in pregnancy, although remarkably similar, varies slightly based on the trimester of pregnancy. Atenolol and verapamil are effective methods of treating SVT, which can be used during the second and third trimesters. Both medications are contraindicated in the first trimester. At the same time, intravenous adenosine can be used in all three trimesters, including labor. Electrical cardioversion is an effective treatment method for hemodynamically unstable or drug-refractory patients, which has proven to be safe in all three trimesters, including labor but can result in pre-term labor in the third trimester. Non-fluoroscopic ablation proved to be the only treatment method that definitively resolved SVT without recurrence.

Diagnostic Scores and Treatment Options for Acute Disseminated Intravascular Coagulation in Children.

Disseminated intravascular coagulation (DIC) is a thrombo-hemorrhagic condition that commonly accompanies life-threatening illnesses in children and is associated with significant morbidity and mortality. Treatment of underlying conditions, hemodynamic support, and replacement therapy with blood components is the mainstay of DIC management. Limited research studies have supported the use of antithrombin (AT), recombinant thrombomodulin (rTM), and protein C concentrates (PrCC). Although there have been several studies and advancements in the DIC treatment in adults, data in pediatric patients are limited, and the consensus is lacking. Evidence validating the use of diagnostic scoring systems in the pediatric population is also limited. Since the hemostatic system differs significantly in children, especially in neonates, management of DIC is also different in children from that of adults, and there is a dire need for good quality research studies in this aspect. We reviewed more than 100 articles in PubMed, Cochrane database, and Google Scholar. This traditional review article discusses different scoring systems for diagnosing DIC in pediatric patients, and different pharmacological treatment options for acute DIC in this population. This study mainly focuses on papers published from 1990 to 2021 and includes papers in all languages involving humans only.

A Systematic Review of Effects of Vitamin E on the Cardiovascular System.

Vitamin E is a fat-soluble vitamin and an antioxidant that prevents the peroxidation of lipid in vitro. The antioxidant role of vitamin E in preventing adverse cardiovascular outcomes is controversial as some studies support it, while others reject it. Therefore, this review aims to determine whether there is an association between vitamin E and cardiovascular diseases (CVDs). An electronic search was done to find out relevant articles. Papers were shortlisted after the initial title and abstract screen. A full-text study was done, and inclusion and exclusion criteria were applied before the quality assessment of each paper was done. Only high-quality papers were selected for analysis. Full-text articles of the last ten years were included, while non-English articles, gray literature, and animal studies were excluded. The majority of the papers, including 75% of the total population in this review, suggested no role of vitamin E in preventing CVD and CVD mortality. Some studies also suggested that a high level of vitamin E can be associated with adverse cardiovascular outcomes. Thus, one should be prudent about taking vitamin E supplementation for cardiovascular risk prevention.

In The Line of Treatment: A Systematic Review of Paroxysmal Supraventricular Tachycardia.

Paroxysmal supraventricular tachycardia (PSVT) is a common tachyarrhythmia, and an electrocardiogram is the best tool for making a diagnosis. If Valsalva maneuvers and carotid sinus massage do not give positive results, then the next choice is either adenosine or calcium channel blockers. At this time, adenosine is the drug of choice of treatment. Verapamil and diltiazem are the most commonly used calcium channel blockers (CCBs). This review aimed to compare the efficacy of both drugs in the treatment of PSVT. We utilized the databases PubMed Central and Medline by using keywords: "calcium channel blockers OR adenosine AND supraventricular tachycardia." In the end, we finalized 32 studies, including observational studies, literature reviews, systematic reviews/metanalysis, and randomized control trials. We included articles only in the English language and related to humans. Two authors completed the quality assessment and evaluation of bias according to specific guidelines. Only high-quality studies were included in this systematic review based on the cut-off score of seven or above. Calcium channel blockers have a longer half-life than adenosine and were previously used as the drug of choice in the treatment of PSVT. Calcium channel blockers are safe if given slowly; however, adenosine is safer and useful when an electrocardiogram is uncertain. We compared both drugs in certain aspects and found equal efficacy. Though safer, adenosine was found to have a higher cost and a higher probability of re-initiation arrhythmia compared to calcium channel blockers.

The Role of Chimeric Antigen Receptor-T Cell Therapy in the Treatment of Hematological Malignancies: Advantages, Trials, and Tribulations, and the Road Ahead.

Immunotherapy is the upcoming trend in cancer treatment. Traditional cancer treatment methods include surgical resection, radiotherapy, chemotherapy, small molecule targeted drugs, monoclonal antibodies, and hematopoietic stem cell transplantation (HSCT). Surgical resection is useful for early-stage patients but not for metastatic cancer cells; radiotherapy and chemotherapy are more common but produce substantial damage to normal tissues and have poor selectivity. Targeted drugs, including monoclonal antibodies, have better comprehensive efficacy but can also encourage gene mutation of tumor cells and drug tolerance. HSCT is effective, but choosing a donor is often difficult, and the graft is also prone to rejection. Thus, chimeric antigen receptor (CAR)-T cell therapy, a form of cellular/adoptive immunotherapy, is at the forefront of cancer therapy treatments due to its sustained remission, fewer side effects, and a better quality of life. CAR-T cell therapy involves genetically modifying the T cells and multiplying their numbers to kill cancer cells. This review article gives an insight into how the CAR-T cells have evolved from simple T cells with modest immune function to genetically engineered robust counterparts that brought great hope in the treatment of hematological malignancies. Much research has been undertaken during the past decade to design and deliver CAR-T cells. This has led to successful outcomes in leukemias, lymphomas, and multiple myeloma, paving the way for expanding CAR therapy. Despite tremendous progress, CAR-T cell therapies are faced with many challenges. Areas for improvement include limited T cell persistence, tumor escape, immunosuppressive components in the tumor microenvironment, cancer relapse rate, manufacturing time, and production cost. In this manuscript, we summarize the innovations in the design and delivery of CAR technologies, their applications in hematological malignancies, limitations to its widespread application, latest developments, and the future scope of research to counter the challenges and improve its effectiveness and persistence.

Cardiovascular Manifestations in Inflammatory Bowel Disease: A Systematic Review of the Pathogenesis and Management of Pericarditis.

Inflammatory bowel disease (IBD) is a chronic condition of the bowel that can be further categorized into ulcerative colitis and Crohn's disease. Rarely, this condition can be associated with pericarditis, which can be an extraintestinal manifestation of the disease or drug-induced. This review aims to determine the pathogenesis and management of pericarditis in IBD. In this review, the goal is to elucidate the pathogenesis of pericarditis in IBD and determine if pericarditis is an extraintestinal manifestation of IBD or a complication of current drug therapy used to manage IBD. Additionally, this review intends to explain the first-line management of pericarditis in IBD and explore the role of biologicals in attenuating pericarditis. An electronic search was conducted to identify relevant reports of pericarditis in IBD, and a quality assessment was conducted to identify high-quality articles according to the inclusion criteria. Full-text articles from inception to November 2020 were included, while non-English articles, gray literature, and animal studies were excluded. The majority of studies suggest that pericarditis arises as a complication of drug therapy by 5-aminosalicylic acid derivatives such as sulfasalazine, mesalamine, and balsalazide, and it occurs due to IgE-mediated allergic reactions, direct cardiac toxicity, cell-mediated hypersensitivity reactions, and humoral antibody response to therapy. Drug cessation or the initiation of a corticosteroid regimen seems to be the most effective means of managing pericarditis in IBD due to drug therapy or an extraintestinal manifestation.

The Importance of Sphingosine Kinase in Breast Cancer: A Potential for Breast Cancer Management.

Breast cancer management includes a combination of surgery, radiation therapy, and chemotherapy. While this management has proven effective, it is not perfect. To expand the umbrella of management to resistant breast cancer tumors, researchers have explored the idea of sphingosine kinase (SphK) and sphingosine-1-phosphate (S1P) as a potential target for treatment. In this article, we review the mechanism of the sphingosine kinase/sphingosine-1-phosphate (SphK/S1P) axis along with its effect on the tumor microenvironment (TME) and compounds that have been studied inhibiting the SphK/S1P axis. We searched for relevant articles in the last five years in Medline and PubMed Central. Inclusion criteria, exclusion criteria, and quality checklists were applied to identify the most relevant articles. We compiled the information that has been summarized in the respective tables and figures provided in this review. The metabolism of sphingolipids was summarized, followed by the SphK/S1P upregulation in breast cancer cells. The variety of effects by upregulation of SphK led to an increase in inflammation, growth, and metastasis in breast cancer tumors. The increase in S1P also impacted the TME, including the cells and surrounding tissue, allowing the breast tumors to thrive. The final point made was a summary of the compounds and drugs that inhibited the SphK/S1P axis. They have proven their effectiveness and show even greater efficacy in combination with docetaxel and doxorubicin in preclinical studies. In conclusion, what is known about the SphK/S1P axis within breast cancer cells is immense but incomplete as we summarize what is known so far. Having a complete picture will allow a faster transition to application in the clinical field but clinical trials have not commenced as of yet.

The Impact of Low Hemoglobin Levels on Cognitive Brain Functions.

The prevalence of dementia is around 5% worldwide in people above 65 years, which increases with aging. Alzheimer's disease is the most common cause of dementia in the elderly. On the other hand, anemia is considered one of the most prevalent comorbidities in the elderly with a prevalence of 11% in those above the age of 65. It is crucial that we find the association between anemia and dementia, as this linkage can prove beneficial. Many currently conducted studies support the idea that anemia is a significant risk factor for dementia. However, some studies still consider anemia and dementia as just an aging process, nothing more. In our study, we found that there are a lot of theories, such as low brain hemoglobin associated with low oxygen levels, which leads to neuron damage. One article mentioned that it is dependent on the level of hemoglobin as an effect with mild to moderate anemia, but apparent with severe forms of it. Researchers are expected to further explore and identify the exact relationship between anemia and dementia. We used the PubMed database as the principal source for data search and extracted articles exploring the relationship and role of anemia in decreasing the cognitive brain functions in the elderly. We reviewed 35 different articles, including clinical trials, review papers, randomized controlled trials (RCTs), and original research published between 2010 and 2020 to find commonly accepted pathophysiology that highlights how anemia causes a decrease in cognitive brain functions.

Similarities Between Depression and Neurodegenerative Diseases: Pathophysiology, Challenges in Diagnosis and Treatment Options.

Depressive disorder and neurodegenerative diseases are two different clinical entities. Depression is a common psychiatric disorder in the general population. However, when present concomitantly with neurodegenerative disorders, its diagnosis becomes challenging. In many cases, patients remain undiagnosed and hence, untreated, worsening the prognosis of the neurodegenerative diseases and impairing the quality of life. One of the possible reasons for the difficulties in diagnosis in such cases is that both conditions affect the central nervous system, so there might be an overlap of symptoms leading to a missed diagnosis of depression in a neurodegenerative disease patient and vice versa. Symptoms such as irritability, apathy, and decreased cognition are common to both types of disorders. Some neurodegenerative diseases, especially Alzheimer's disease, can initially present as a depressive prodrome. This may cause a difficulty in differentiating between these two conditions and a diagnosis of either conditions may be missed; hence an opportunity for timely intervention and improved outcomes is missed. An approach towards analyzing and comparing the pathological mechanisms common to both disease types will create a better understanding of depression and neurodegenerative diseases, identify their similarities, and develop improved clinical criteria to help clinicians make a timely diagnosis of these conditions present together. In the present review, various studies related to common pathological links, concomitant diagnosis challenges, and ongoing research about different treatment options are discussed.

Multiple Sclerosis and Serotonin: Potential Therapeutic Applications.

Multiple sclerosis (MS) is a neurodegenerative disease with a complex autoimmune component, and it has a high prevalence among middle-aged females. The manifestations of the disease range from episodic somatosensory dysfunction to progressive and permanent central nervous system (CNS) damage. Due to a high prevalence of psychiatric comorbidities and proven abnormalities in serotonin (5-HT) levels among MS patients, they are usually on drugs that modify the serotonergic system. Through a comprehensive literature review of studies published in the last 10 years related to 5-HT in MS and its therapeutic applications, we aimed to elucidate the mechanism behind the neurotransmitter (NT) levels' abnormalities. Most importantly, we endeavored to gather the most up-to-date information about the full therapeutic potential of agents acting on this system. We discovered that multiple processes cause low levels of 5-HT in MS patients. The varying levels of the availability of the 5-HT transporter (SERT) in the CNS decreasing overall tryptophan (TRP) levels, and diversion of the amino acid away from its synthetic pathway constitute some of those. Studies in animals have shown that 5-HT levels' elevations could cause immune-modulating effects and could probably slow down the disease progression rate. Human studies have shown a more diverse and complex response. Promising results have been obtained in the last 10 years regarding 5-HT's immune-modulatory role in MS patients and its therapeutic applications. Human studies with a larger population and feasible designs are still needed to fully ascertain the effects of serotonin on the immune system and disease progression in patients with MS.

Statins Versus Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors- Are We Doing Better? A Systematic Review on Treatment Disparity.

Coronary artery disease (CAD) is a significant contributor to mortality in America. A common risk factor of CAD is hyperlipidemia. Treatment guidelines of hyperlipidemia are well established. Statins are the cornerstone of treating hyperlipidemia. New medications such as proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9 inhibitors) have also illustrated significant results in treating hyperlipidemia. While multiple studies exemplify the disparities in statin and PCSK9 inhibitors utilization to reduce CAD mortality and risk factors, there are no systematic reviews to validate these disparities. We conducted a search on PubMed, including Medline and PubMed Central, and Google Scholar. For this analysis, we selected articles published between 2000 and 2020 and those that fit the inclusion and exclusion criteria. Based on the type of study, we performed appropriate quality assessments and deleted studies with a score of less than seven or with a high risk of biases. The search strategy resulted in 322 studies. After inclusion and exclusion criteria were applied, we included 20 articles in the analysis of this review. This systematic review demonstrates that non-white races and women were less likely to receive the correct, clinically indicated, therapy for hyperlipidemia. A multi-faceted approach is required to solve this inequality in healthcare.

Pacemaking Activity in the Peripheral Nervous System: Physiology and Roles of Hyperpolarization Activated and Cyclic Nucleotide-Gated Channels in Neuropathic Pain.

The most famous pacemaking activity found in the human body is in the cardiac system. However, pacemaking is also widely present in the nervous system. The ion channels responsible for the pacemaking activity are called hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels. HCN channels are activated during hyperpolarization and create an inward current named Ih containing mixed sodium and potassium ions. The molecular mechanism of these unique features remains mysterious. In the peripheral nervous system (PNS), pacemaking is unique because it is only present in pathologic states when nerve damage occurs and leads to neuropathic pain. For this reason, pacemaking in neuropathic pain is also known as ectopic discharge. In our literature review, the HCN channel physiology is one of the research interests. We will present studies exploring the molecular mechanisms involved in HCN gating and ion permeability. The second research question is, what makes the pacemaking activity unique in the PNS? Thus, our paper will include studies that discuss the role of HCN channels in neuropathic pain. Given the fundamental role of HCN channels in regulating neuronal cells' discharge activity, the modulation of their function for therapeutic purposes could be useful in various pathological conditions. Here we review the present knowledge of the efficacy of HCN blocker treating neuropathic pain in humans.

The Sickle Effect: The Silent Titan Affecting Glycated Hemoglobin Reliability.

Hemoglobin A1c (HbA1c) is a popular invaluable tool in the diagnosis of Type 2 diabetes for red blood cells (RBCs) with a lifespan of 120 days; however, many factors, including hemoglobinopathies, affect its accuracy. Sickle cell trait, primarily a benign medical condition, is a point mutation in only one of two beta-globin genes on chromosome 11. We performed a traditional review to identify how the sickle cell trait (SCT) affects the interpretation of HbA1c and the further implications it may have on the diagnosis and management of Type 2 diabetes. A literature search was performed using PubMed®/MEDLINE® and Google Scholar with formulated keywords (sickle cell trait, HbAS, HbA1c, glycosylated hemoglobin, diabetes, RBC lifespan, race, and genetics), with the majority of results being mainly observational studies. The National Glycohemoglobin Standardization Program (NGSP) is responsible for standardizing HbA1c results and also highlights factors that can interfere with HbA1c, including hemoglobin variants. Studies that utilize only an NGSP-certified method with no clinically significant interference by HbS in patients with and without SCT showed contrasting results. Additional studies showed that persons of African ancestry, the group to which the majority of SCT patients belong, have a higher HbA1c than non-Hispanic whites (NHWs), just based on race, and a greater probability of having glucose-6-phosphate dehydrogenase (G6PD) deficiency, which lowers HbA1c. The most extensive study investigating the RBC lifespan in SCT patients showed a reduction in the cell lifespan compared to normal patients; however, other smaller studies were contradictory. Our study highlights the need for hemoglobinopathy detection before or during HbA1c measurement in populations with a high degree of African ancestry and the importance of patient notification. It also shows that SCT affects the accuracy of HbA1c, through its likely reduction of RBC lifespan and its increased association with African ancestry and G6PD deficiency. This review recommends that for SCT patients with potential Type 2 diabetes, HbA1c should be used in combination with another diagnostic tool such as fasting blood glucose, fructosamine, or glycated albumin to decrease the chances of a missed diagnosis.