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Innovations in Clinical Neuroscience Nov 2019Clozapine-induced agranulocytosis, malignant hyperthermia (MH), statin-induced myopathy, and neuroleptic malignant syndrome (NMS) are all serious drug reactions with... (Review)
Review
Clozapine-induced agranulocytosis, malignant hyperthermia (MH), statin-induced myopathy, and neuroleptic malignant syndrome (NMS) are all serious drug reactions with significant overlap in terms of clinical symptomatology. The use of clozapine can lead to neutropenia, as well as the development of NMS; thus, it seemed logical to explore a possible common genetic background for the development of these two adverse effects. Furthermore, due to the overwhelming clinical resemblance between NMS, MH, and statin-induced myopathy, we decided specifically to search for a common genetic background in the development of these conditions. We searched the PubMed, OMIM, WikiGenes, Medline, and Google Scholar databases to identify articles pertinent to our subject published over the last 30 years. Articles were reviewed according to our inclusion/exclusion criteria, and irrelevant articles were excluded. In our exploration for a common genetic background between clozapine-induced agranulocytosis, MH, NMS, and statin-induced myopathy, we identified the SLCO1B1 gene, which was common to three of these four conditions (MH, statin-induced myopathy, and clozapine-induced agranulocytosis). Although we did not find a gene common among NMS and the other conditions, the overlap of clinical symptoms between NMS, MH, and statin-induced myopathy did not allow us to rule out the possibility of a common factor, in terms of genetic predisposition, between these conditions. Future studies can aid to fill in the gaps of knowledge in terms of any genetic linkage between these three conditions and the mechanism of their associations.
PubMed: 32082940
DOI: No ID Found -
Pharmacogenomics Jan 2020Pharmacogenetics, the genetic influence on the interpersonal variability in drug response, has enabled tailored pharmacotherapy and emerging 'personalized medicine.'... (Review)
Review
Pharmacogenetics, the genetic influence on the interpersonal variability in drug response, has enabled tailored pharmacotherapy and emerging 'personalized medicine.' Although oncology spearheaded the clinical implementation of personalized medicine, other specialties are rapidly catching up. In anesthesia, classical examples of genetically mediated idiosyncratic reactions have been long known (e.g., malignant hyperthermia and prolonged apnea after succinylcholine). The last two decades have witnessed an expanding body of pharmacogenetic evidence in anesthesia. This review highlights some of the prominent pharmacogenetic associations studied in anesthesia and pain management, with special focus on pediatric anesthesia.
Topics: Anesthesia; Anesthesiology; Apnea; Child; Child, Preschool; Humans; Malignant Hyperthermia; Pain; Pain Management; Pediatrics; Precision Medicine; Succinylcholine
PubMed: 31849281
DOI: 10.2217/pgs-2019-0108 -
Biomaterials Research Nov 2023Malignant bone tumors are characterized by severe disability rate, mortality rate, and heavy recurrence rate owing to the complex pathogenesis and insidious disease... (Review)
Review
Malignant bone tumors are characterized by severe disability rate, mortality rate, and heavy recurrence rate owing to the complex pathogenesis and insidious disease progression, which seriously affect the terminal quality of patients' lives. Photothermal therapy (PTT) has emerged as an attractive adjunctive treatment offering prominent hyperthermal therapeutic effects to enhance the effectiveness of surgical treatment and avoid recurrence. Simultaneously, various advanced biomaterials with photothermal capacity are currently created to address malignant bone tumors, performing distinctive biological functions, including nanomaterials, bioceramics (BC), polymers, and hydrogels et al. Furthermore, PTT-related combination therapeutic strategies can provide more significant curative benefits by reducing drug toxicity, improving tumor-killing efficiency, stimulating anti-cancer immunity, and improving immune sensitivity relative to monotherapy, even in complex tumor microenvironments (TME). This review summarizes the current advanced biomaterials applicable in PTT and relevant combination therapies on malignant bone tumors for the first time. The multiple choices of advanced biomaterials, treatment methods, and new prospects for future research in treating malignant bone tumors with PTT are generalized to provide guidance. Malignant bone tumors seriously affect the terminal quality of patients' lives. Photothermal therapy (PTT) has emerged as an attractive adjunctive treatment enhancing the effectiveness of surgical treatment and avoiding recurrence. In this review, advanced biomaterials applicable in the PTT of malignant bone tumors and their distinctive biological functions are comprehensively summarized for the first time. Simultaneously, multiple PTT-related combination therapeutic strategies are classified to optimize practical clinical issues, contributing to the selection of biomaterials, therapeutic alternatives, and research perspectives for the adjuvant treatment of malignant bone tumors with PTT in the future.
PubMed: 37968707
DOI: 10.1186/s40824-023-00453-z -
Medicine Aug 2021Malignant hyperthermia (MH) and exertional rhabdomyolysis (ERM) have long been considered episodic phenotypes occurring in response to external triggers in otherwise...
INTRODUCTION
Malignant hyperthermia (MH) and exertional rhabdomyolysis (ERM) have long been considered episodic phenotypes occurring in response to external triggers in otherwise healthy individuals with variants in RYR1. However, recent studies have demonstrated a clinical and histopathological continuum between patients with RYR1-related congenital myopathies and those with ERM or MH susceptibility. Furthermore, animal studies have shown non-neuromuscular features such as a mild bleeding disorder and an immunological gain-of-function associated with MH/ERM related RYR1 variants raising important questions for further research. Awareness of the neuromuscular disease spectrum and potential multisystem involvement in RYR1-related MH and ERM is essential to optimize the diagnostic work-up, improve counselling and and future treatment strategies for patients affected by these conditions. This study will examine in detail the nature and severity of continuous disease manifestations and their effect on daily life in patients with RYR1-related MH and ERM.
METHODS
The study protocol consists of four parts; an online questionnaire study, a clinical observational study, muscle imaging, and specific immunological studies. Patients with RYR1-related MH susceptibility and ERM will be included. The imaging, immunological and clinical studies will have a cross-sectional design, while the questionnaire study will be performed three times during a year to assess disease impact, daily living activities, fatigue and pain. The imaging study consists of muscle ultrasound and whole-body magnetic resonance imaging studies. For the immunological studies, peripheral mononuclear blood cells will be isolated for in vitro stimulation with toll-like receptor ligands, to examine the role of the immune system in the pathophysiology of RYR1-related MH and ERM.
DISCUSSION
This study will increase knowledge of the full spectrum of neuromuscular and multisystem features of RYR1-related MH and ERM and will establish a well-characterized baseline cohort for future studies on RYR1-related disorders. The results of this study are expected to improve recognition of RYR1-related symptoms, counselling and a more personalized approach to patients affected by these conditions. Furthermore, results will create new insights in the role of the immune system in the pathophysiology of MH and ERM.
TRIAL REGISTRATION
This study was pre-registered at ClinicalTrials.gov (ID: NCT04610619).
Topics: Clinical Protocols; Cohort Studies; Cross-Sectional Studies; Humans; Malignant Hyperthermia; Prospective Studies; Rhabdomyolysis; Ryanodine Receptor Calcium Release Channel; Surveys and Questionnaires
PubMed: 34414986
DOI: 10.1097/MD.0000000000026999 -
Cureus Apr 2024As a result of the widespread prevalence of anesthetic usage, anesthesia-related complications are well studied, ranging from benign postoperative nausea and vomiting to... (Review)
Review
As a result of the widespread prevalence of anesthetic usage, anesthesia-related complications are well studied, ranging from benign postoperative nausea and vomiting to potentially fatal complications, such as paralysis, malignant hyperthermia, and death. However, one intersection that still needs further analysis is the relationship between vector-borne illnesses (VBIs) and anesthetic complications. With the advent of climate change and global warming, what were previously endemic vectors have spread far beyond their typical regions, resulting in the spread of VBI. As the incidence of VBIs rapidly increases in the United States, operations for diagnostic testing, and thus the identification and treatments of these VBIs, have significantly diminished. A literature review was conducted to analyze case reports of patients with VBIs and anesthetic concerns with sources from PubMed and Google Scholar databases, and a wide range of complications were found.
PubMed: 38586230
DOI: 10.7759/cureus.57517 -
Journal of Anaesthesiology, Clinical... 2019
PubMed: 31920247
DOI: 10.4103/joacp.JOACP_243_18 -
Orphanet Journal of Rare Diseases May 2020Pathogenic variations in the gene encoding the skeletal muscle ryanodine receptor (RyR1) are associated with malignant hyperthermia (MH) susceptibility, a... (Review)
Review
BACKGROUND
Pathogenic variations in the gene encoding the skeletal muscle ryanodine receptor (RyR1) are associated with malignant hyperthermia (MH) susceptibility, a life-threatening hypermetabolic condition and RYR1-related myopathies (RYR1-RM), a spectrum of rare neuromuscular disorders. In RYR1-RM, intracellular calcium dysregulation, post-translational modifications, and decreased protein expression lead to a heterogenous clinical presentation including proximal muscle weakness, contractures, scoliosis, respiratory insufficiency, and ophthalmoplegia. Preclinical model systems of RYR1-RM and MH have been developed to better understand underlying pathomechanisms and test potential therapeutics.
METHODS
We conducted a comprehensive scoping review of scientific literature pertaining to RYR1-RM and MH preclinical model systems in accordance with the PRISMA Scoping Reviews Checklist and the framework proposed by Arksey and O'Malley. Two major electronic databases (PubMed and EMBASE) were searched without language restriction for articles and abstracts published between January 1, 1990 and July 3, 2019.
RESULTS
Our search yielded 5049 publications from which 262 were included in this review. A majority of variants tested in RYR1 preclinical models were localized to established MH/central core disease (MH/CCD) hot spots. A total of 250 unique RYR1 variations were reported in human/rodent/porcine models with 95% being missense substitutions. The most frequently reported RYR1 variant was R614C/R615C (human/porcine total n = 39), followed by Y523S/Y524S (rabbit/mouse total n = 30), I4898T/I4897T/I4895T (human/rabbit/mouse total n = 20), and R163C/R165C (human/mouse total n = 18). The dyspedic mouse was utilized by 47% of publications in the rodent category and its RyR1-null (1B5) myotubes were transfected in 23% of publications in the cellular model category. In studies of transfected HEK-293 cells, 57% of RYR1 variations affected the RyR1 channel and activation core domain. A total of 15 RYR1 mutant mouse strains were identified of which ten were heterozygous, three were compound heterozygous, and a further two were knockout. Porcine, avian, zebrafish, C. elegans, canine, equine, and drosophila model systems were also reported.
CONCLUSIONS
Over the past 30 years, there were 262 publications on MH and RYR1-RM preclinical model systems featuring more than 200 unique RYR1 variations tested in a broad range of species. Findings from these studies have set the foundation for therapeutic development for MH and RYR1-RM.
Topics: Animals; Caenorhabditis elegans; Dogs; HEK293 Cells; Horses; Humans; Hyperthermia; Malignant Hyperthermia; Mice; Muscular Diseases; Mutation; Rabbits; Ryanodine Receptor Calcium Release Channel; Swine; Zebrafish
PubMed: 32381029
DOI: 10.1186/s13023-020-01384-x -
Anesthesiology and Pain Medicine Feb 2023Neuromuscular diseases (NMDs) are regarded as a clinically and genetically heterogeneous group of diseases characterized by weakening muscle strength and dystrophic... (Review)
Review
CONTEXT
Neuromuscular diseases (NMDs) are regarded as a clinically and genetically heterogeneous group of diseases characterized by weakening muscle strength and dystrophic changes in the muscle. Due to the nature of these diseases, it can be challenging for anesthesiologists to provide appropriate pain medications, symptom management, and other necessary techniques that are implemented to anesthetize the patient properly.
EVIDENCE ACQUISITION
This study was based on the available literature and the authors' experience. The current study aimed to review the available anesthesia for patients suffering from NMDs. The search process resulted in the detection of relevant articles using valid keywords on electronic databases, including Embase, PubMed, Scopus, Web of Science, and Cochrane Library. Subsequently, 19 articles published between 2009 to 2022 were identified as eligible for this review.
RESULTS
When anesthetizing a patient with NMD, special attention should be paid to preoperative evaluation, medical-history taking, risk of difficult intubation or cardiac incidents, respiratory insufficiency, and frequent pulmonary infections. It is also necessary to keep in mind that these patients are at risk of prolonged paralysis, hyperkalemia, rigidity, malignant hyperthermia, cardiac arrest, rhabdomyolysis, or even death.
CONCLUSIONS
Problems of anesthesia in patients with NMDs arise from the nature of the condition itself and the interaction of anesthetics and muscle relaxants with anticholinesterase drugs used in therapy. Each patient's individual risk should be assessed before anesthesia. Therefore, it is important (and even necessary before major surgery) to perform a thorough preoperative examination to not only determine perioperative risk but also to ensure optimal perioperative follow-up.
PubMed: 37409004
DOI: 10.5812/aapm-132088 -
Radiation Oncology (London, England) Sep 2022Soft tissue sarcomas (STS) represent a diverse group of rare malignant tumors. Currently, five to six weeks of preoperative radiotherapy (RT) combined with surgery... (Review)
Review
BACKGROUND
Soft tissue sarcomas (STS) represent a diverse group of rare malignant tumors. Currently, five to six weeks of preoperative radiotherapy (RT) combined with surgery constitute the mainstay of therapy for localized high-grade sarcomas (G2-G3). Growing evidence suggests that shortening preoperative RT courses by hypofractionation neither increases toxicity rates nor impairs oncological outcomes. Instead, shortening RT courses may improve therapy adherence, raise cost-effectiveness, and provide more treatment opportunities for a wider range of patients. Presumed higher rates of adverse effects and worse outcomes are concerns about hypofractionated RT (HFRT) for STS. This systematic review summarizes the current evidence on preoperative HFRT for the treatment of STS and discusses toxicity and oncological outcomes compared to normofractionated RT.
METHODS
We conducted a systematic review of clinical trials describing outcomes for preoperative HFRT in the management of STS using PubMed, the Cochrane library, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, Embase, and Ovid Medline. We followed the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Trials on retroperitoneal sarcomas, postoperative RT, and hyperthermia were excluded. Articles published until November 30th, 2021, were included.
RESULTS
Initial search yielded 94 articles. After removal of duplicate and ineligible articles, 13 articles qualified for analysis. Eight phase II trials and five retrospective analyses were reviewed. Most trials applied 5 × 5 Gy preoperatively in patients with high-grade STS. HFRT courses did not show increased rates of adverse events compared to historical trials of normofractionated RT. Toxicity rates were mostly comparable or lower than in trials of normofractionated RT. Moreover, HFRT achieved comparable local control rates with shorter duration of therapy. Currently, more than 15 prospective studies on HFRT + / - chemotherapy are ongoing.
CONCLUSIONS
Retrospective data and phase II trials suggest preoperative HFRT to be a reasonable treatment modality for STS. Oncological outcomes and toxicity profiles were favorable. To date, our knowledge is mostly derived from phase II data. No randomized phase III trial comparing normofractionated and HFRT in STS has been published yet. Multiple ongoing phase II trials applying HFRT to investigate acute and late toxicity will hopefully bring forth valuable findings.
Topics: Humans; Prospective Studies; Radiation Dose Hypofractionation; Retrospective Studies; Sarcoma; Soft Tissue Neoplasms
PubMed: 36104789
DOI: 10.1186/s13014-022-02072-9 -
Brazilian Journal of Anesthesiology... 2023Malignant Hyperthermia (MH) is a pharmacogenetic disorder triggered by halogenated anesthesia agents/succinylcholine and characterized by hypermetabolism crisis during... (Observational Study)
Observational Study
BACKGROUND
Malignant Hyperthermia (MH) is a pharmacogenetic disorder triggered by halogenated anesthesia agents/succinylcholine and characterized by hypermetabolism crisis during anesthesia, but also by day-to-day symptoms, such as exercise intolerance, that may alert the health professional.
OBJECTIVE
The study aimed to analyze the incidence of fatigue in MH susceptible patients and the variables that can impact perception of fatigue, such as the level of routine physical activity and depression.
METHODS
A cross-sectional observational study was carried out with three groups ... 22 patients susceptible to MH (positive in vitro muscle contracture test), 13 non-susceptible to MH (negative in vitro muscle contracture test) and 22 controls (no history of MH). Groups were assessed by a demographic/clinical questionnaire, a fatigue severity scale (intensity, specific situations, psychological consequences, rest/sleep response), and the Beck depression scale. Subgroups were re-assessed with the Baecke habitual physical exercise questionnaire (occupational physical activity, leisure physical exercise, leisure/locomotion physical activity).
RESULTS
There were no significant differences among the three groups regarding fatigue intensity, fatigue related to specific situations, psychological consequences of fatigue, fatigue response to resting/sleeping, depression, number of active/sedentary participants, and the mean time and characteristics of habitual physical activity. Nevertheless, unlike the control sub-group, the physically active MH-susceptible subgroup had a higher fatigue response to resting/sleeping than the sedentary MH susceptible subgroup (respectively, 5.9.ß...ß1.9 vs. 3.9.ß...ß2, t-test unpaired, p.ß<.ß0.05).
CONCLUSION
We did not detect subjective fatigue in MH susceptible patients, although we reported protracted recovery after physical activity, which may alert us to further investigation requirements.
Topics: Humans; Malignant Hyperthermia; Halothane; Cross-Sectional Studies; Depression; Contracture; Exercise; Disease Susceptibility
PubMed: 34626754
DOI: 10.1016/j.bjane.2021.07.038