Neuroblastoma: Essential genetic pathways and current therapeutic options.

Neuroblastoma is a very diverse pediatric tumor that starts from the neural crest, and it is responsible over more than 15% of all juvenile cancer deaths. Clinical signs and symptoms are highly dependent on tumor origin and spread. Bone, lymph nodes, liver, intracranial and orbital tissues, lungs, and the central nervous system are frequently involved in metastatic neuroblastoma. Neuroblastoma enhances with contrast in Computed Tomography (CT) scans as a solid heterogeneous mass which might invade to adjacent ipsilateral or contralateral lymph nodes, tissues, and vessels. Whereas the Magnetic Resonance Imaging (MRI) acquires an acceptable diagnostic accuracy for detection of spinal cord and musculoskeletal metastases. Lorlatinib, a novel ALK inhibitor designed to overcome this resistance, is currently being tested in the New Approaches to Neuroblastoma Therapy (NANT) consortium. Aurora kinase inhibitors have been reported to disrupt MYCN, which is particularly attractive considering the lack of direct inhibitors targeting this driver in neuroblastoma. Sorafenib, a RAF kinase inhibitor, and newer PI3K inhibitors are being tested in children with neuroblastoma in an attempt to block the RAS pathway. Despite various therapies including chemotherapy, radiotherapy, immunotherapy and autologous stem cell transplantation in different neuroblastoma risk groups, most patients undergo surgical removal of the tumoral mass. This review is aimed to summarize the updated knowledge about the neuroblastoma, pathogenesis, it's essential genetic pathways and the current available therapeutic options for neuroblastoma.

The association of Takotsubo cardiomyopathy and aneurysmal subarachnoid hemorrhage: A U.S. nationwide analysis.

OBJECTIVE: Takotsubo cardiomyopathy (TC) is a stress-induced cardiomyopathy that can be precipitated by aneurysmal subarachnoid hemorrhage (aSAH). Several studies have shown patients who develop TC following aSAH have an increased risk of disability and mortality. The goal of this study is to examine the incidence of TC in aSAH, identify its risk factors, and analyze its impact on patient outcomes. METHODS: Data for patients with aSAH between the years of 2009 and 2018 were extracted from the Nationwide Inpatient Sample (NIS) and stratified based on the diagnosis of TC. Univariate analysis was used to assess the incidence of TC and covariates including patient demographics, aneurysmal treatment, in-hospital mortality rate, length of stay and costs. Multivariate logistic regression models analyzed the relationship between TC and these variables RESULTS: 80,915 aSAH patient-discharges were included in this study, 673 (0.83%) of which, developed TC. Females (OR 3.49, CI [2.82-4.33], P < 0.001), white ethnicity (69% vs 63%, P = 0.003) and patients with certain comorbidities including smoking (OR 1.64, CI [1.38-1.95], P < 0.0001) and seizures (OR 1.32, CI [1.07, 1.64], P = 0.01) were most likely to develop TC. Patients who developed TC had significantly increased mortality (OR 1.36, CI [1.13-1.65], P = 0.001), hospital stays (mean days of 19.4 vs 11.5, P < 0.0001), and costs ($104,111 vs $48,734, P < 0.0001). Hypertension (OR 0.63, CI [0.54-0.74], P < 0.0001) and hyperlipidemia (OR 0.63, CI [0.51-0.77], P < 0.0001) were found to be protective against TC. Patients with TC after acute SAH were more likely to undergo endovascular coiling (OR 1.68, CI [1.327-2.127], P < 0.001) rather than surgical clipping (OR 0.66, CI [0.52-0.83], P < 0.0001). CONCLUSIONS: Female sex, white ethnicity, smoking and seizures represented significant predictors of developing TC after aSAH, while hypercholesterolemia and hypertension were protective.

Paroxysmal sympathetic hyperactivity during traumatic brain injury.

Traumatic brain injury (TBI) is one of the leading causes of disability, morbidity, and mortality worldwide. Some of the more common etiologies of TBI include closed head injury, penetrating head injury, or an explosive blast head injury. Neuronal damage in TBI is related to both primary injury (caused by mechanical forces), and secondary injury (caused by the subsequent tissue and cellular damages). Recently, it has been well established that Paroxysmal Sympathetic Hyperactivity (PSH), also known as "Sympathetic Storm", is one of the main causes of secondary neuronal injury in TBI patients. The clinical manifestations of PSH include recurrent episodes of sympathetic hyperactivity characterized by tachycardia, systolic hypertension, hyperthermia, tachypnea with hyperpnea, and frank diaphoresis. Given the diverse manifestations of PSH and its notable impact on the outcome of TBI patients, we have comprehensively reviewed the current evidence and discussed the pathophysiology, clinical manifestations, time of onset and duration of PSH during TBI. This article reviews the different types of head injuries that most commonly lead to PSH, possible approaches to manage and minimize PSH complications in TBI and the current prognosis and outcomes of PSH in TBI patients.

Parasite-based interventions in systemic lupus erythematosus (SLE): A systematic review.

BACKGROUND: The hygiene hypothesis proposed in 1989 expresses that allergic and infectious diseases are inversely related. Accordingly, it has been demonstrated that infection with some microorganisms such as parasites and helminths can provide a potential immunity and prevent the onset of some life-threatening autoimmune diseases like systemic lupus erythematosus (SLE). Therefore, in this comprehensive study, we systematically reviewed and discussed the use of live parasites or parasitic products in the treatment of mouse models of SLE. METHODS: The present systematic review was performed using the following search terms: ("systemic lupus erythematosus" OR "SLE" OR "lupus") AND ("parasite" OR "protozoa" OR "helminths" OR "worms" OR "helminth" OR "worm") in PubMed, Scopus, and Web of Science online databases. We included studies reporting the effect of any intervention using parasites or parasitic-based products on animal models of SLE, which were published until January 20th, 2021 without any language or date restrictions. For each included study, we extracted the authors' names, publication year, type of animal, number of groups, types of intervention, sample size, changes in immunologic cells, auto-Abs, cytokines, and blood cells count, urine analysis, histological analysis of kidney/spleen/liver, outcome and survival. (PROSPERO CRD42020160460). RESULTS: A total of 17 eligible articles were included in this systematic review. Sixteen out of the 17 studies reported immunomodulating changes in immunologic cells, cytokines, and/or auto-Abs in mouse models of SLE after using parasitic interventions compared to not-infected or control groups. Moreover, 14 studies reported decreased level of proteinuria and/or favorable kidney, liver, or spleen histological changes. CONCLUSION: In conclusion, we have demonstrated that parasites like Hymenolepis microstoma, TPC and ES-62 from Acanthocheilonema viteae, Plasmodium chabaudi, Schistosoma mansoni, and Toxoplasma gondii have favorable immunomodulating effects on SLE outcomes in lupus-prone mice.

Molecular Biomarkers in Multiple Sclerosis and Its Related Disorders: A Critical Review.

Multiple sclerosis (MS) is a chronic autoimmune disease affecting the central nervous system (CNS) which can lead to severe disability. Several diseases can mimic the clinical manifestations of MS. This can often lead to a prolonged period that involves numerous tests and investigations before a definitive diagnosis is reached. As well as the possibility of misdiagnosis. Molecular biomarkers can play a unique role in this regard. Molecular biomarkers offer a unique view into the CNS disorders. They help us understand the pathophysiology of disease as well as guiding our diagnostic, therapeutic, and prognostic approaches in CNS disorders. This review highlights the most prominent molecular biomarkers found in the literature with respect to MS and its related disorders. Based on numerous recent clinical and experimental studies, we demonstrate that several molecular biomarkers could very well aid us in differentiating MS from its related disorders. The implications of this work will hopefully serve clinicians and researchers alike, who regularly deal with MS and its related disorders.