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1.
MANAGEMENT OF ENDOCRINE DISEASE: Cardiovascular risk assessment, thromboembolism, and infection prevention in Cushing's syndrome: a practical approach.
Varlamov, EV, Langlois, F, Vila, G, Fleseriu, M
European journal of endocrinology. 2021;(5):R207-R224
Abstract
Cushing's syndrome (CS) is associated with increased mortality that is driven by cardiovascular, thromboembolic, and infection complications. Although these events are expected to decrease during disease remission, incidence often transiently increases postoperatively and is not completely normalized in the long-term. It is important to diagnose and treat cardiovascular, thromboembolic, and infection complications concomitantly with CS treatment. Management of hyperglycemia/diabetes, hypertension, hypokalemia, hyperlipidemia, and other cardiovascular risk factors is generally undertaken in accordance with clinical care standards. Medical therapy for CS may be needed even prior to surgery in severe and/or prolonged hypercortisolism, and treatment adjustments can be made based on disease pathophysiology and drug-drug interactions. Thromboprophylaxis should be considered for CS patients with severe hypercortisolism and/or postoperatively, based on individual risk factors of thromboembolism and bleeding. Pneumocystis jiroveci pneumonia prophylaxis should be considered for patients with high urinary free cortisol at the initiation of hypercortisolism treatment.
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2.
New-onset refractory status epilepticus and febrile infection-related epilepsy syndrome.
Specchio, N, Pietrafusa, N
Developmental medicine and child neurology. 2020;(8):897-905
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Abstract
New-onset refractory status epilepticus (NORSE) and febrile infection-related epilepsy syndrome (FIRES) are relatively rare clinical presentations. They are characterized by de novo onset of refractory status epilepticus (RSE) without clearly identifiable acute or active cause (structural, toxic, or metabolic). We reviewed the literature using PubMed reports published between 2003 and 2019 and summarized the clinical, neurophysiological, imaging, and treatment findings. Focal motor seizures, which tend to evolve into status epilepticus, characterize the typical presentation. Disease course is biphasic: acute phase followed by chronic phase with refractory epilepsy and neurological impairment. Aetiology is unknown, but immune-inflammatory-mediated epileptic encephalopathy is suspected. Electroencephalograms show variety in discharges (sporadic or periodic, focal, generalized, or more frequently bilateral), sometimes with a multifocal pattern. About 70% of adult NORSE have abnormal magnetic resonance imaging (MRI); in paediatric series of FIRES, 61.2% of patients have a normal brain MRI at the beginning and only 18.5% during the chronic phase. No specific therapy for FIRES and NORSE currently exists; high doses of barbiturates and ketogenic diet can be used with some effectiveness. Recently, anakinra and tocilizumab, targeting interleukin pathways, have emerged as potential specific therapies. Mortality rate is around 12% in children and even higher in adults (16-27%).
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Rhinacanthus nasutus "Tea" Infusions and the Medicinal Benefits of the Constituent Phytochemicals.
Brimson, JM, Prasanth, MI, Malar, DS, Brimson, S, Tencomnao, T
Nutrients. 2020;(12)
Abstract
Rhinacanthus nasutus (L.) Kurz (Acanthaceae) (Rn) is an herbaceous shrub native to Thailand and much of South and Southeast Asia. It has several synonyms and local or common names. The root of Rn is used in Thai traditional medicine to treat snake bites, and the roots and/or leaves can be made into a balm and applied to the skin for the treatment of skin infections such as ringworm, or they may be brewed to form an infusion for the treatment of inflammatory disorders. Rn leaves are available to the public for purchase in the form of "tea bags" as a natural herbal remedy for a long list of disorders, including diabetes, skin diseases (antifungal, ringworm, eczema, scurf, herpes), gastritis, raised blood pressure, improved blood circulation, early-stage tuberculosis antitumor activity, and as an antipyretic. There have been many studies investigating the roles of Rn or compounds isolated from the herb regarding diseases such as Alzheimer's and other neurodegenerative diseases, cancer, diabetes and infection with bacteria, fungi or viruses. There have, however, been no clinical trials to confirm the efficacy of Rn in the treatment of any of these disorders, and the safety of these teas over long periods of consumption has never been tested. This review assesses the recent research into the role of Rn and its constituent compounds in a range of diseases.
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Neurocritical care and target immunotherapy for febrile infection-related epilepsy syndrome.
Sakuma, H, Horino, A, Kuki, I
Biomedical journal. 2020;(3):205-210
Abstract
Febrile infection-related epilepsy syndrome (FIRES) is an intractable neurological disease characterized by an unexplained refractory status epilepticus triggered by febrile infection. A Consensus definition of FIRES was proposed in 2018, and its clinical features and prognosis are gradually being clarified. However, the development of effective treatments has been hindered as the etiology of this rare disease is as yet unelucidated. The basic approach to the management of FIRES, like other forms of epilepsy, is based on the control of seizures, however seizures are extremely intractable and require intravenous administration of large doses of anticonvulsants, mainly barbiturates. This treatment strategy produces various complications including respiratory depression and drug hypersensitivity syndrome, which make it more difficult to control seizures. Consequently, it is crucial to predict these events and to formulate a planned treatment strategy. As well, it is important to grow out of conventional treatment strategies that rely on only anticonvulsants, and alternative therapies are gradually being developed. One such example is the adoption of a ketogenic diet which may lead to reduced convulsions as well as improve intellectual prognosis. Further, overproduction of inflammatory cytokines in the central nervous system has been shown to be strongly related to the pathology of FIRES which has led to attempts at immunomodulation therapy including anti-cytokine therapy.
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Free Amino Acids in Human Milk: A Potential Role for Glutamine and Glutamate in the Protection Against Neonatal Allergies and Infections.
van Sadelhoff, JHJ, Wiertsema, SP, Garssen, J, Hogenkamp, A
Frontiers in immunology. 2020;:1007
Abstract
Breastfeeding is indicated to support neonatal immune development and to protect against neonatal infections and allergies. Human milk composition is widely studied in relation to these unique abilities, which has led to the identification of various immunomodulating components in human milk, including various bioactive proteins. In addition to proteins, human milk contains free amino acids (FAAs), which have not been well-studied. Of those, the FAAs glutamate and glutamine are by far the most abundant. Levels of these FAAs in human milk sharply increase during the first months of lactation, in contrast to most other FAAs. These unique dynamics are globally consistent, suggesting that their levels in human milk are tightly regulated throughout lactation and, consequently, that they might have specific roles in the developing neonate. Interestingly, free glutamine and glutamate are reported to exhibit immunomodulating capacities, indicating that these FAAs could contribute to neonatal immune development and to the unique protective effects of breastfeeding. This review describes the current understanding of the FAA composition in human milk. Moreover, it provides an overview of the effects of free glutamine and glutamate on immune parameters relevant for allergic sensitization and infections in early life. The data reviewed provide rationale to study the role of free glutamine and glutamate in human milk in the protection against neonatal allergies and infections.
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Infectious complications of newer agents in the fight against diabetes.
Stover, KR, Hugh, E, Sherman, JJ, Malinowski, SS, Berdahl, GJ, Riche, DM
The Nurse practitioner. 2020;(11):17-24
Abstract
Infectious complications have been reported with antidiabetic medications. Glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors have been associated with upper respiratory tract infections and urinary tract infections. Sodium-glucose cotransporter 2 inhibitors have been associated with lower limb amputations, urinary tract infections, genital mycotic infections, and Fournier gangrene.
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The Role of the Adipokine Leptin in Immune Cell Function in Health and Disease.
Kiernan, K, MacIver, NJ
Frontiers in immunology. 2020;:622468
Abstract
Leptin is a critical mediator of the immune response to changes in overall nutrition. Leptin is produced by adipocytes in proportion to adipose tissue mass and is therefore increased in obesity. Despite having a well-described role in regulating systemic metabolism and appetite, leptin displays pleiotropic actions, and it is now clear that leptin has a key role in influencing immune cell function. Indeed, many immune cells have been shown to respond to leptin directly via the leptin receptor, resulting in a largely pro-inflammatory phenotype. Understanding the role of adipose-tissue derived mediators in inflammation is critical to determining the pathophysiology of multiple obesity-associated diseases, such as type 2 diabetes, autoimmune disease, and infection. This review, therefore, focuses on the latest data regarding the role of leptin in modulating inflammation.
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Managing Risks with Biologics.
Click, B, Regueiro, M
Current gastroenterology reports. 2019;(2):1
Abstract
PURPOSE OF REVIEW With a rapidly evolving complement of advanced targeted therapies in inflammatory bowel disease, additional safety and side effect concerns emerge. It is the purpose of this review to consider various risks with biologic therapies in inflammatory bowel disease and discuss mitigating strategies. RECENT FINDINGS Two recently approved monoclonal antibodies (vedolizumab and ustekinumab) and a Janus kinase inhibitor small molecule (tofacitnib) have introduced a number of novel safety and risk considerations. We review the clinical trial and real-world safety data to date on these agents as well as review new data and considerations with anti-tumor necrosis factor agents. New vaccines for varicella zoster virus, hepatitis B virus, and high-dose influenza have been studied, and we discuss the clinical importance of these findings. Lastly, we make management recommendations in the event of particular side effects or complications. Understanding the risks of new agents in inflammatory bowel disease, potential mitigating strategies, and management considerations is important to achieving and maintaining clinical outcomes in IBD patients.
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9.
Role of Glutathionylation in Infection and Inflammation.
Checconi, P, Limongi, D, Baldelli, S, Ciriolo, MR, Nencioni, L, Palamara, AT
Nutrients. 2019;(8)
Abstract
Glutathionylation, that is, the formation of mixed disulfides between protein cysteines and glutathione (GSH) cysteines, is a reversible post-translational modification catalyzed by different cellular oxidoreductases, by which the redox state of the cell modulates protein function. So far, most studies on the identification of glutathionylated proteins have focused on cellular proteins, including proteins involved in host response to infection, but there is a growing number of reports showing that microbial proteins also undergo glutathionylation, with modification of their characteristics and functions. In the present review, we highlight the signaling role of GSH through glutathionylation, particularly focusing on microbial (viral and bacterial) glutathionylated proteins (GSSPs) and host GSSPs involved in the immune/inflammatory response to infection; moreover, we discuss the biological role of the process in microbial infections and related host responses.
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10.
Intrauterine infection, immune system and premature birth.
Helmo, FR, Alves, EAR, Moreira, RAA, Severino, VO, Rocha, LP, Monteiro, MLGDR, Reis, MAD, Etchebehere, RM, Machado, JR, Corrêa, RRM
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. 2018;(9):1227-1233
Abstract
Preterm birth accounts for nearly one million deaths among children under five years of age, and although its etiopathogenesis is not fully elucidated, ascending intrauterine infection and fetal inflammatory response seem to be the main triggers. The intense inflammatory response mediated by IL-1β, TNF-α, PAF, IFN-γ and IL-6, PGE2 and MMP-1 and MMP-9 causes fetal membrane damage and rupture, increased uterine contractions and biochemical and structural changes in the cervix. Furthermore, preterm neonates have deficient innate and adaptive immune responses characterized by reduced levels of IgG, opsonization and phagocytosis, as well as increased activation of Th1 cells in relation to Th2 cells. Therefore, this triad is favors the occurrence of neonatal complications, such as respiratory distress syndrome, necrotizing enterocolitis, retinopathy of prematurity and bronchopulmonary dysplasia. Due to serious maternal and child health complications of intrauterine infection, several studies have tried to identify biomarkers for the early diagnosis of this entity. This literature review aims to discuss the main scientific findings regarding the association between ascending intrauterine infection, immune system and preterm birth.