Glioblastoma, an opportunity T cell trafficking could bring for the treatment.

PURPOSE: Infiltrating into the vital structure of the brain, located in the inaccessible anatomical region, and having molecular heterogeneity, glioblastoma (GBM) -with no doubt- is one of the deadliest cancers. Using the blood and brain barrier (BBB), GBM makes a shield to restrict the reach of chemotherapeutic agents to the tumor site and evolves a unique microenvironment to furnish all the essentials for cancer cells survival to conceal neoplastic cells from immunosurveillance. METHODS: 99 papers which met the criteria of eligibility were included in this review by consensus. The included articles were classified based on their design and level of evidence. RESULTS: Given this characteristic, immunotherapies for a while enjoyed unprecedented attention as a solution for GBM treatment; however, it did not take long before the enthusiasm for their application was muted. It became apparent that cancer cells intelligently find a way to manipulate the anti-tumor responses of agents by attracting immunosuppressive lymphocytes into the brain using the lymphatic vessels. This event makes GBM a good model for immunotherapy resistance. However, the presence of lymphatic vessels has fired up an idea of the adoptive attraction of effector T lymphocytes to the tumor milieu. This was when engineering and cloning technologies, which have given life to one of the recent treatment strategies using artificial T cells named chimeric antigen receptors (CAR) T-cells, came to action to design specific CAR T-cells for the treatment of GBM. CONCLUSION: The present review summarizes the recent advances in CAR T-cell-based treatments in GBM and discusses why this approach could be positioned as a pillar of the next-generation of immunotherapies for this type of brain tumor.

Idiopathic intracranial hypertension associated with polycystic ovarian syndrome, sensorineural hearing loss, and elevated inflammatory markers that lead to bilateral blindness: A case report with literature review.

Background: Pseudotumor cerebri (PTC) or idiopathic intracranial hypertension (IIH) is characterized by elevated intracranial pressure without hydrocephalus or mass lesion, with normal cerebrospinal fluid (CSF) studies and neuroimaging. The exact cause remains uncertain, but potential mechanisms include increased CSF production, impaired CSF absorption, cerebral edema, and abnormal cerebral venous pressure gradients. Patients may present with various accompanying symptoms such as unilateral or bilateral visual obscuration, pulsatile tinnitus, back pain, dizziness, neck pain, blurred vision, cognitive difficulties, radicular pain, and typically intermittent horizontal diplopia. Case Description: We report a case of a 32-year-old female who initially presented with chronic headaches and oligomenorrhea, which resulted in the diagnosis of polycystic ovary syndrome (PCOS) a few years before the initial diagnosis of PTC. Despite receiving maximum medical treatment and undergoing optic nerve sheath fenestration, the patient experienced complete bilateral vision loss. Nearly 5 years later, the patient sought care at our outpatient neurology clinic, presenting with symptoms including tinnitus, left-sided hearing loss, and joint pain with elevated inflammatory markers and headaches. The focus of this research was to discuss the pathophysiology of each of these comorbidities. Conclusion: This case report aims to explore the pathophysiological relationships between PTC and concurrent comorbidities, including PCOS, sensorineural hearing loss, empty sella (ES) syndrome, and elevated inflammatory markers. Remarkably, no other PTC case with this unique constellation of concurrent comorbidities have been reported in existing medical literature. The case report underscores the critical importance of early diagnosis of IIH and prompt medical intervention, particularly in patients with PCOS experiencing chronic headaches.

Maternal and fetal exposure to metal (loid)s, maternal nutrition status, and impact on prenatal growth in an energy rich zone and an urban area along the Persian Gulf.

The main purposes of the study were to determine whether maternal and cord blood (MB and CB) levels of metal (loid)s (MLs) are different between industrial and urban areas. Subjects were derived from the petrochemical and gas area (PGA) of Asaluyeh County and the urban area (UA) of Bushehr County in Iran. Adjusted models revealed significant differences between the PGA and UA for maternal Fe, Cu, Mg, Cd, Zn, Ni, V and Pb levels, likewise cord Cu, V, Pb and Ni levels, which were higher in the PGA. Unadjusted models revealed there were decreases in neonatal weight and head circumference by 16.550 g and 0.059 cm, respectively for each Ln unit increase in maternal Cr levels. The mean blood levels of MLs significantly associated with food consumption frequency. The MLs were detected at higher levels in the body's fetuses and their mothers who resided in the PGA than those from the UA. So, the fetuses of mothers living in an industrial areas may be at higher risk from anthropometric measures. The impact of prenatal exposure to MLs on prenatal growth should be considered for better understanding in the further studies.

Acute Bilateral Blindness in the Setting of Sudden Onset of Bilateral Proptosis and Ophthalmoplegia: A Case Report With Literature Review.

PURPOSE OF REVIEW: Acute bilateral blindness has an extensive differential diagnosis that requires a careful history and physical examination to narrow down. In this article, we discuss the pathophysiology and radiographic findings of each possible diagnosis for acute bilateral blindness. RECENT FINDINGS: Visual pathology with respect to bilateral blindness can be broadly broken down into 3 anatomic categories: media (i.e., the anterior and posterior chamber of the eye), retina, and neural visual pathway. Possible causes of rapid onset bilateral blindness include bilateral occipital infarcts, endogenous bacterial endophthalmitis, orbital cellulitis, orbital compartment syndrome, cavernous sinus thrombophlebitis, thyroid disease, and bilateral nonarteritic ischemic optic neuropathy. SUMMARY: In this case, we present a patient with acute onset of bilateral blindness, in addition to bilateral ophthalmoplegia, proptosis, and orbital chemosis. We believe that this rare case of acute bilateral blindness is thought provoking and aids in the understanding of the differential diagnosis and underlying pathophysiology of visual loss.

Oversized primary intrapulmonary schwannoma: A case report and a review of the literature.

BACKGROUND: Schwannomas, also known as neurilemommas, are benign, well-circumscribed encapsulated peripheral nerve sheath tumors with rather indolent evolution. Made up of cells closely related to normal myelinating Schwann cells, these neoplasms may arise from the peripheral nervous system as well as from spinal or cranial nerves. They are mostly found in the base of the skull, neck, chest wall, posterior mediastinum, posterior spinal roots, cerebellopontine angle, retroperitoneum, and flexor surfaces of the extremities. The incidence rate of spinal schwannoma is 0.3-0.5/100,000 cases per year with an average age of 50 at diagnosis. We report a case of intrapulmonary schwannoma, adding a review of the literature. CASE DESCRIPTION: A 20-year-old female patient with no significant medical history, presented with pleuritic chest pain, shortness of breath, right upper limb weakness, and numbness. A computed tomography of the chest and magnetic resonance imaging showed a 7.2 × 10.5 × 8.3 cm mass in the posterior segment of the right upper lobe, arising from the right T5-6 neural foramen; a concurrent 16 mm thick right pleural effusion was also noticed yet without evidence of nodular enhancement. The findings suggested the presence of a neurofibroma or a schwannoma. Complete resection of the tumor was achieved through posterolateral thoracotomy; the ensuing histopathological and immunohistochemical examinations confirmed the presence of a schwannoma. CONCLUSION: We believe this rare case of pulmonary invasive schwannoma illustrates the complex dynamics of this extremely rare entity; in this particular case, complete surgical excision proved to be crucial in terms of subacute management and local tumor control, at least at short and middle term. The patient is currently asymptomatic (6 months postsurgery) and remains on follow-up.

Immunoglobulin E as a Biomarker for the Overlap of Atopic Asthma and Chronic Obstructive Pulmonary Disease.

Asthma-COPD overlap (ACO) is a common clinical syndrome, yet there is no single objective definition. We hypothesized that immunoglobulin E (IgE) measurements could be used to refine the definition of ACO. In baseline plasma samples from 2870 participants in the COPD Genetic Epidemiology (COPDGene®) study, we measured total IgE levels and specific IgE levels to 6 common allergens. Compared to usual chronic obstructive pulmonary disease (COPD), participants with ACO (based on self-report of asthma) had higher total IgE levels (median 67.0 versus 42.2 IU/ml) and more frequently had at least one positive specific IgE (43.5% versus 24.5%). We previously used a strict definition of ACO in participants with COPD, based on self-report of a doctor's diagnosis of asthma before age 40. This strict ACO definition was refined by the presence of atopy, determined by total IgE > 100 IU/ml or at least one positive specific IgE, as was the broader definition of ACO based on self-reported asthma history. Participants with all 3 ACO definitions were younger (mean age 60.0-61.3 years), were more commonly African American (36.8%-44.2%), had a higher exacerbation frequency (1.0-1.2 in the past year), and had more airway wall thickening on quantitative analysis of chest computed tomography (CT) scans. Among participants with ACO, 37%-46% did not have atopy; these individuals had more emphysema on chest CT scan. Based on associations with exacerbations and CT airway disease, IgE did not clearly improve the clinical definition of ACO. However, IgE measurements could be used to subdivide individuals with atopic and non-atopic ACO, who might have different biologic mechanisms and potential treatments.

A Web-Based Pharmacogenomics Search Tool for Precision Medicine in Perioperative Care.

Background: Precision medicine represents an evolving approach to improve treatment efficacy by modifying it to individual patient's gene variation. Pharmacogenetics, an applicable branch of precision medicine, identifies patient's predisposing genotypes that alter the clinical outcome of the drug, hence preventing serious adverse drug reactions. Pharmacogenetics has been extensively applied to various fields of medicine, but in the field of anesthesiology and preoperative medicine, it has been unexploited. Although the US Food and Drug Administration (FDA) has a table of pharmacogenomics biomarkers and pharmacogenetics, this table only includes general side effects of the included drugs. Thus, the existing FDA table offers limited information on genetic variations that may increase drug side effects. Aims: The purpose of this paper is to provide a web-based pharmacogenomics search tool composed of a comprehensive list of medications that have pharmacogenetic relevance to perioperative medicine that might also have application in other fields of medicine. Method: For this investigation, the FDA table of pharmacogenomics biomarkers in drug labeling was utilized as an in-depth of drugs to construct our pharmacogenetics drug table. We performed a literature search for drug-gene interactions using the unique list of drugs in the FDA table. Publications containing the drug-gene interactions were identified and reviewed. Additional drugs and extracted gene-interactions in the identified publications were added to the constructed drug table. Result: Our tool provides a comprehensive pharmacogenetic drug table including 258 drugs with a total of 461 drug-gene interactions and their corresponding gene variations that might cause modifications in drug efficacy, pharmacokinetics, pharmacodynamics and adverse reactions. This tool is freely accessible online and can be applied as a web-based search instrument for drug-gene interactions in different fields of medicine, including perioperative medicine. Conclusion: In this research, we collected drug-gene interactions in a web-based searchable tool that could be used by physicians to expand their field knowledge in pharmacogenetics and facilitate their clinical decision making. This precision medicine tool could further serve in establishing a comprehensive perioperative pharmacogenomics database that also includes different fields of medicine that could influence the outcome of perioperative medicine.

Impact of delayed treatment on exacerbations of multiple sclerosis among Puerto Rican patients.

BACKGROUND: There are limited data on multiple sclerosis (MS) patients in underserved groups, including Puerto Rico. In this study, we analyzed the characteristic of MS symptoms and number of relapses in Puerto Rican patients. We then compare these characteristics with MS patients from the US. The number of MS relapses is highly correlated with the treatment onset and adherence. Patients in Puerto Rico have been experiencing lengthy treatment delay. We will discuss the possible causes of such delay and its impact on MS prognosis. METHODS: This retrospective cohort study consisted of the evaluation of 325 medical records from MS patients attending the Caribbean Neurological Center from 2014 to 2019. We gathered symptoms and comorbidities data as binary objects. The treatment delay was calculated based on the mean value of days between diagnosis and treatment onset for these groups of patients. RESULTS: We found that on average, the treatment delay for MS patients in Puerto Rico (PR) to receive their medication was 120 days. The most common MS subtype was relapsing-remitting 72.8%, with a mean of 1.684 relapses per year. Initial symptoms were sensory 54%, visual 33.1%, motor 28.8%, coordination 23.2%, fatigue 9.7%, memory 7.3%, depression 6.5%, urinary 4.9%, gastrointestinal 2.4%, and sexual dysfunction 1.6%. The most common comorbidities were hypertension 18.4%, asthma 13.6%, and thyroid disease 12.8%. When we compared the comorbidities between the two populations, immune thrombocytopenia had the highest percent change with the value of almost 200% (0.001% of US patient vs. 0.8% of Puerto Rican MS patients). CONCLUSION: Patients from Puerto Rico had a 33% higher relapse rate compared to the one reported for MS patients in the US. This higher rate may be related to the long delay in receiving their medications. They also had a higher rate of complex comorbidities such as immune thrombocytopenia or thyroid disease. Our findings provide a proof of concept that delay in receiving medications can increase the number of relapses and complex comorbidities among MS patients.

Comprehensive review of neuromyelitis optica and clinical characteristics of neuromyelitis optica patients in Puerto Rico.

Neuromyelitis optica (NMO) is an immune-mediated inflammatory disorder of the central nervous system. It is characterized by concurrent inflammation and demyelination of the optic nerve (optic neuritis [ON]) and the spinal cord (myelitis). Multiple studies show variations in prevalence, clinical, and demographic features of NMO among different populations. In addition, ethnicity and race are known as important factors on disease phenotype and clinical outcomes. There are little data on information about NMO patients in underserved groups, including Puerto Rico (PR). In this research, we will provide a comprehensive overview of all aspects of NMO, including epidemiology, environmental risk factors, genetic factors, molecular mechanism, symptoms, comorbidities and clinical differentiation, diagnosis, treatment, its management, and prognosis. We will also evaluate the demographic features and clinical phenotype of NMO patients in PR. This will provide a better understanding of NMO and establish a basis of knowledge that can be used to improve care. Furthermore, this type of population-based study can distinguish the clinical features variation among NMO patients and will provide insight into the potential mechanisms that cause these variations.

Subtyping Chronic Obstructive Pulmonary Disease Using Peripheral Blood Proteomics.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disorder. COPD patients may have different clinical features, imaging characteristics and natural history. Multiple studies have investigated heterogeneity using statistical methods such as unsupervised clustering to define different subgroups of COPD based largely on clinical phenotypes. Some studies have performed clustering using genetic data or limited numbers of blood biomarkers. Our primary goal was to use proteomic data to find subtypes of COPD within clinically similar individuals. In the Treatment of Emphysema with a gamma-Selective Retinoid Agonist (TESRA) study, multiplex biomarker panels were run in serum samples collected prior to randomization. After implementing an algorithm to minimize missing values, the dataset included 396 COPD individuals and 87 biomarkers. Using hierarchical clustering, we identified 3 COPD subgroups, containing 267 (67.4%), 104 (26.3%), and 25 (6.3%) individuals, respectively. The third cluster had less emphysema on quantitative analysis of chest computed tomography scans (p=0.03) and worse disease-related quality of life based on the St. George's Respiratory Questionnaire (total score cluster 1: 45.6, cluster 2: 45.4, cluster 3: 56.6; p=0.01), despite similar levels of lung function impairment (forced expiratory volume in 1 second (49.2%, 49.2%, 48.2 % predicted, respectively). Enrichment analysis showed the biomarkers distinguishing cluster 3 mapped to platelet alpha granule and cell chemotaxis pathways. Thus, we identified a subgroup which has less emphysema but may have greater inflammation, which could be potentially targeted with anti-inflammatory therapies.

A comprehensive review of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a late-onset fatal neurodegenerative disease affecting motor neurons with an incidence of about 1/100,000. Most ALS cases are sporadic, but 5-10% of the cases are familial ALS. Both sporadic and familial ALS (FALS) are associated with degeneration of cortical and spinal motor neurons. The etiology of ALS remains unknown. However, mutations of superoxide dismutase 1 have been known as the most common cause of FALS. In this study, we provide a comprehensive review of ALS. We cover all aspects of the disease including epidemiology, comorbidities, environmental risk factor, molecular mechanism, genetic factors, symptoms, diagnostic, treatment, and even the available supplement and management of ALS. This will provide the reader with an advantage of receiving a broad range of information about the disease.

Stochastic tracking of infection in a CF lung.

Magnetic Resonance Imaging (MRI) and Computed Tomography (CT) scan are the two ubiquitous imaging sources that physicians use to diagnose patients with Cystic Fibrosis (CF) or any other Chronic Obstructive Pulmonary Disease (COPD). Unfortunately the cost constraints limit the frequent usage of these medical imaging procedures. In addition, even though both CT scan and MRI provide mesoscopic details of a lung, in order to obtain microscopic information a very high resolution is required. Neither MRI nor CT scans provide micro level information about the location of infection in a binary tree structure the binary tree structure of the human lung. In this paper we present an algorithm that enhances the current imaging results by providing estimated micro level information concerning the location of the infection. The estimate is based on a calculation of the distribution of possible mucus blockages consistent with available information using an offline Metropolis-Hastings algorithm in combination with a real-time interpolation scheme. When supplemented with growth rates for the pockets of mucus, the algorithm can also be used to estimate how lung functionality as manifested in spirometric tests will change in patients with CF or COPD.

Mucus distribution model in a lung with cystic fibrosis.

Cystic fibrosis (CF) is the most common autosomal recessive disease in Caucasians with a reported incidence of 1 in every 3200 live births. Most strikingly, CF is associated with early mortality. Host in flammatory responses result in airway mucus plugging, airway wall edema, and eventual destruction of airway wall support structure. Despite aggressive treatment, the median age of survival is approximately 38 years. This work is the first attempt to parameterize the distributions of mucus in a CF lung as a function of time. By default, the model makes arbitrary choices at each stage of the construction process, whereby the simplest choice is made. The model is sophisticated enough to fit the average CF patients' spirometric data over time and to identify several interesting parameters: probability of colonization, mucus volume growth rate, and scarring rate. Extensions of the model appropriate for describing the dynamics of single patient MRI data are also discussed.