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Pharmacology 2023Glioblastoma multiforme (GBM) is a WHO grade 4 glioma and the most common malignant primary brain tumour. Recently, there has been outstanding progress in the treatment... (Review)
Review
BACKGROUND
Glioblastoma multiforme (GBM) is a WHO grade 4 glioma and the most common malignant primary brain tumour. Recently, there has been outstanding progress in the treatment of GBM. In addition to the newest form of GBM removal using fluorescence, three-dimensional (3D) imaging, tomoradiotherapy, moderate electro-hyperthermia, and adjuvant temozolomide (post-operative chemotherapy), new developments have been made in the fields of immunology, molecular biology, and virotherapy. An unusual and modern treatment has been created, especially for stage 4 GBM, using the latest therapeutic techniques, including immunotherapy and virotherapy. Modern oncological medicine is producing extraordinary and progressive therapeutic methods. Oncological therapy includes individual analysis of the properties of a tumour and targeted therapy using small-molecule inhibitors. Individualised medicine covers the entire patient (tumour and host) in the context of immunotherapy. An example is individualised multimodal immunotherapy (IMI), which relies on individual immunological tumour-host interactions. In addition, IMI is based on the concept of oncolytic virus-induced immunogenic tumour cell death.
SUMMARY
In this review, we outline current knowledge of the various available treatment options used in the therapy of GBM including both traditional therapeutic strategy and modern therapies, such as tomotherapy, electro-hyperthermia, and oncolytic virotherapy, which are promising treatment strategies with the potential to improve prognosis in patients with GBM.
KEY MESSAGES
This newest therapy, immunotherapy combined with virotherapy (oncolytic viruses and cancer vaccines), is displaying encouraging signs for combating GBM. Additionally, the latest 3D imaging is compared to conventional two-dimensional imaging.
Topics: Humans; Glioblastoma; Glioma; Oncolytic Virotherapy; Temozolomide; Brain Neoplasms
PubMed: 37459849
DOI: 10.1159/000531319 -
Anaesthesia May 2021Malignant hyperthermia is defined in the International Classification of Diseases as a progressive life-threatening hyperthermic reaction occurring during general...
Malignant hyperthermia is defined in the International Classification of Diseases as a progressive life-threatening hyperthermic reaction occurring during general anaesthesia. Malignant hyperthermia has an underlying genetic basis, and genetically susceptible individuals are at risk of developing malignant hyperthermia if they are exposed to any of the potent inhalational anaesthetics or suxamethonium. It can also be described as a malignant hypermetabolic syndrome. There are no specific clinical features of malignant hyperthermia and the condition may prove fatal unless it is recognised in its early stages and treatment is promptly and aggressively implemented. The Association of Anaesthetists has previously produced crisis management guidelines intended to be displayed in all anaesthetic rooms as an aide memoire should a malignant hyperthermia reaction occur. The last iteration was produced in 2011 and since then there have been some developments requiring an update. In these guidelines we will provide background information that has been used in updating the crisis management recommendations but will also provide more detailed guidance on the clinical diagnosis of malignant hyperthermia. The scope of these guidelines is extended to include practical guidance for anaesthetists dealing with a case of suspected malignant hyperthermia once the acute reaction has been reversed. This includes information on care and monitoring during and after the event; appropriate equipment and resuscitative measures within the operating theatre and ICU; the importance of communication and teamwork; guidance on counselling of the patient and their family; and how to make a referral of the patient for confirmation of the diagnosis. We also review which patients presenting for surgery may be at increased risk of developing malignant hyperthermia under anaesthesia and what precautions should be taken during the peri-operative management of the patients.
Topics: Acidosis; Body Temperature; Calcium; Carbon Dioxide; Compartment Syndromes; Dantrolene; Disseminated Intravascular Coagulation; Heart Rate; Humans; Hyperkalemia; Malignant Hyperthermia; Muscle Relaxants, Central; Myoglobinuria; Pulmonary Ventilation; Risk Factors; Sodium Bicarbonate
PubMed: 33399225
DOI: 10.1111/anae.15317 -
Journal of Applied Physiology... Nov 2019During the past several decades, the incidence of exertional heat stroke (EHS) has increased dramatically. Despite an improved understanding of this syndrome, numerous... (Review)
Review
During the past several decades, the incidence of exertional heat stroke (EHS) has increased dramatically. Despite an improved understanding of this syndrome, numerous controversies still exist within the scientific and health professions regarding diagnosis, pathophysiology, risk factors, treatment, and return to physical activity. This review examines the following eight controversies: ) reliance on core temperature for diagnosing and assessing severity of EHS; ) hypothalamic damage induces heat stroke and this mediates "thermoregulatory failure" during the immediate recovery period; ) EHS is a predictable condition primarily resulting from overwhelming heat stress; ) heat-induced endotoxemia mediates systemic inflammatory response syndrome in all EHS cases; ) nonsteroidal anti-inflammatory drugs for EHS prevention; ) EHS shares similar mechanisms with malignant hyperthermia; ) cooling to a specific body core temperature during treatment for EHS; and ) return to physical activity based on physiological responses to a single-exercise heat tolerance test. In this review, we present and discuss the origins and the evidence for each controversy and propose next steps to resolve the misconception.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Body Temperature; Body Temperature Regulation; Cryotherapy; Exercise; Heat Stroke; Humans; Physical Exertion; Risk Factors
PubMed: 31545156
DOI: 10.1152/japplphysiol.00452.2019 -
Cureus Jul 2022Humans maintain core body temperature via a complicated system of physiologic mechanisms that counteract heat/cold fluctuations from metabolism, exertion, and the... (Review)
Review
Humans maintain core body temperature via a complicated system of physiologic mechanisms that counteract heat/cold fluctuations from metabolism, exertion, and the environment. Overextension of these mechanisms or disruption of body temperature homeostasis leads to bodily dysfunction, culminating in a syndrome analogous to exertional heat stroke (EHS). The inability of this thermoregulatory process to maintain the body temperature is caused by either thermal stress or certain drugs. EHS is a syndrome characterized by hyperthermia and the activation of systemic inflammation. Several drug-induced hyperthermic syndromes may resemble EHS and share common mechanisms. The purpose of this article is to review the current literature and compare exertional heat stroke (EHS) to three of the most widely studied drug-induced hyperthermic syndromes: malignant hyperthermia (MH), neuroleptic malignant syndrome (NMS), and serotonin syndrome (SS). Drugs and drug classes that have been implicated in these conditions include amphetamines, diuretics, cocaine, antipsychotics, metoclopramide, selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), and many more. Observations suggest that severe or fulminant cases of drug-induced hyperthermia may evolve into an inflammatory syndrome best described as heat stroke. Their underlying mechanisms, symptoms, and treatment approaches will be reviewed to assist in accurate diagnosis, which will impact the management of potentially life-threatening complications.
PubMed: 36039261
DOI: 10.7759/cureus.27278 -
British Journal of Anaesthesia Jan 2021Malignant hyperthermia is a potentially fatal condition, in which genetically predisposed individuals develop a hypermetabolic reaction to potent inhalation anaesthetics...
Malignant hyperthermia is a potentially fatal condition, in which genetically predisposed individuals develop a hypermetabolic reaction to potent inhalation anaesthetics or succinylcholine. Because of the rarity of malignant hyperthermia and ethical limitations, there is no evidence from interventional trials to inform the optimal perioperative management of patients known or suspected with malignant hyperthermia who present for surgery. Furthermore, as the concentrations of residual volatile anaesthetics that might trigger a malignant hyperthermia crisis are unknown and manufacturers' instructions differ considerably, there are uncertainties about how individual anaesthetic machines or workstations need to be prepared to avoid inadvertent exposure of susceptible patients to trigger anaesthetic drugs. The present guidelines are intended to bundle the available knowledge about perioperative management of malignant hyperthermia-susceptible patients and the preparation of anaesthesia workstations. The latter aspect includes guidance on the use of activated charcoal filters. The guidelines were developed by members of the European Malignant Hyperthermia Group, and they are based on evaluation of the available literature and a formal consensus process. The most crucial recommendation is that malignant hyperthermia-susceptible patients should receive anaesthesia that is free of triggering agents. Providing that this can be achieved, other key recommendations include avoidance of prophylactic administration of dantrolene; that preoperative management, intraoperative monitoring, and care in the PACU are unaltered by malignant hyperthermia susceptibility; and that malignant hyperthermia patients may be anaesthetised in an outpatient setting.
Topics: Anesthesia; Consensus; Europe; Humans; Malignant Hyperthermia; Perioperative Care
PubMed: 33131754
DOI: 10.1016/j.bja.2020.09.029 -
The anaesthetist, opioid analgesic drugs, and serotonin toxicity: a mechanistic and clinical review.British Journal of Anaesthesia Jan 2020Most cases of serotonin toxicity are provoked by therapeutic doses of a combination of two or more serotonergic drugs, defined as drugs affecting the serotonin... (Review)
Review
Most cases of serotonin toxicity are provoked by therapeutic doses of a combination of two or more serotonergic drugs, defined as drugs affecting the serotonin neurotransmitter system. Common serotonergic drugs include many antidepressants, antipsychotics, and opioid analgesics, particularly fentanyl, tramadol, meperidine (pethidine), and methadone, but rarely morphine and other related phenanthrenes. Symptoms of serotonin toxicity are attributable to an effect on monoaminergic transmission caused by an increased synaptic concentration of serotonin. The serotonin transporter (SERT) maintains low serotonin concentrations and is important for the reuptake of the neurotransmitter into the presynaptic nerve terminals. Some opioids inhibit the reuptake of serotonin by inhibiting SERT, thus increasing the plasma and synaptic cleft serotonin concentrations that activate the serotonin receptors. Opioids that are good inhibitors of SERT (tramadol, dextromethorphan, methadone, and meperidine) are most frequently associated with serotonin toxicity. Tramadol also has a direct serotonin-releasing action. Fentanyl produces an efflux of serotonin, and binds to 5-hydroxytryptamine (5-HT) and 5-HT receptors, whilst methadone, meperidine, and more weakly tapentadol, bind to 5-HT but not 5-HT receptors. The perioperative period is a time where opioids and other serotonergic drugs are frequently administered in rapid succession, sometimes to patients with other serotonergic drugs in their system. This makes the perioperative period a relatively risky time for serotonin toxicity to occur. The intraoperative recognition of serotonin toxicity is challenging as it can mimic other serious syndromes, such as malignant hyperthermia, sepsis, thyroid storm, and neuroleptic malignant syndrome. Anaesthetists must maintain a heightened awareness of its possible occurrence and a readiness to engage in early treatment to avoid poor outcomes.
Topics: Analgesics, Opioid; Anesthesiologists; Fever; Humans; Intraoperative Complications; Serotonin Agents; Serotonin Syndrome
PubMed: 31653394
DOI: 10.1016/j.bja.2019.08.010