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Medicine Apr 2024Malignant hyperthermia (MH) is a rare yet serious medical complication that typically arises following general anesthesia or the administration of specific anesthetics....
Diagnosis and rescue of malignant hyperthermia induced by anesthesia during radical surgery in a cervical cancer patient using the National Remote Emergency System: A case report.
RATIONALE
Malignant hyperthermia (MH) is a rare yet serious medical complication that typically arises following general anesthesia or the administration of specific anesthetics. Due to the infrequency of MH, anesthesiologists often lack sufficient expertise in identifying and managing it, leading to misdiagnosis and inappropriate treatment. There is an urgent need to enhance the diagnosis and management of MH through the utilization of relevant tools.
PATIENT CONCERNS
In this case, a 52-year-old woman underwent radical cervical cancer surgery under general anesthesia, with no family or significant medical history. She experienced a gradual increase in end-tidal carbon dioxide (ETCO2) to a maximum of 75 mm Hg and a rise in body temperature from 36.5 to 37.5 °C in a very short period, as well as a blood gas analysis showing a pH of 7.217.
DIAGNOSIS
The anesthesiologist immediately used The WeChat applet-based National Remote Emergency System for Malignant Hyperthermia (MH-NRES), and the score was 40, which indicated that the patient was very likely to have MH.
INTERVENTIONS
We immediately discontinued sevoflurane and switched total intravenous anesthesia to maintain general anesthesia, with a rapid intravenous infusion of dantrolene sodium.
OUTCOMES
The ETCO2 and the temperature quickly dropped to normal, followed by successful completion of the surgery, and the patient was discharged 8 days after surgery.
LESSONS
The experience can provide a basis use of MH-NRES and improve the ability of anesthesiologists to deal with intraoperative MH as well as increase the survival probability of patients.
Topics: Female; Humans; Middle Aged; Malignant Hyperthermia; Uterine Cervical Neoplasms; Dantrolene; Sevoflurane; Anesthesia, General
PubMed: 38640306
DOI: 10.1097/MD.0000000000037699 -
Open Medicine (Warsaw, Poland) 2023Malignant hyperthermia (MH) is an inherited skeletal muscle disorder caused primarily by a genetic mutation, usually in the calcium channel gene of the muscle. This...
Malignant hyperthermia (MH) is an inherited skeletal muscle disorder caused primarily by a genetic mutation, usually in the calcium channel gene of the muscle. This mutation can lead to muscle hypersensitivity to volatile anesthetics (such as sevoflurane) and the depolarizing muscle relaxant succinylcholine, resulting in hyperthermia, muscle stiffness, metabolic disturbances, and other severe physiological reactions. This condition may prove fatal unless it is recognized in its early stages and treatment is administered promptly and aggressively. We report a 13-year-old adolescent who underwent laparoscopic appendectomy and developed MH after the use of inhalational anesthetics, manifested by unremitting hyperthermia with a maximum temperature of 44.2°C, muscle rigidity, tachycardia, hypercapnia; and malignant arrhythmias, cardiogenic shock, hyperkalemia, metabolic, and respiratory acidosis. After early and timely recognition, multidisciplinary management and administration of dantrolene, the case was successfully treated. Exome sequencing revealed a point mutation (amino acid change) on the RYR1 gene: c.12700G>C(p.Val4234Leu). Due to the lack of ready-made dantrolene in our hospital, the patient in this case received dantrolene treatment only 6 h after the first observation of high body temperature. We review the development of the disease and summarize the success of treatment and what can be done to improve the chances of saving the patient's life if dantrolene is not available in time.
PubMed: 37873543
DOI: 10.1515/med-2023-0808 -
ACS Nano Oct 2023Photodynamic therapy (PDT) and photothermal therapy (PTT) have gained considerable attention as potential alternatives to conventional cancer treatments. However, these...
Photodynamic therapy (PDT) and photothermal therapy (PTT) have gained considerable attention as potential alternatives to conventional cancer treatments. However, these approaches remain limited by low solubility, poor stability, and inefficient targeting of many common photosensitizers (PSs) and photothermal agents (PTAs). To overcome the aforementioned limitations, we engineered biocompatible and biodegradable tumor-targeted upconversion nanospheres with imaging capabilities. The multifunctional nanospheres consist of a sodium yttrium fluoride core doped with lanthanides (ytterbium, erbium, and gadolinium) and the PTA bismuth selenide (NaYF:Yb/Er/Gd,BiSe) enveloped in a mesoporous silica shell that encapsulates a PS, chlorin e6 (Ce6), within its pores. NaYF:Yb/Er converts deeply penetrating near-infrared (NIR) light to visible light, which excites Ce6 to generate cytotoxic reactive oxygen species (ROS), while BiSe efficiently converts absorbed NIR light to heat. Additionally, Gd enables magnetic resonance imaging of the nanospheres. The mesoporous silica shell is coated with DPPC/cholesterol/DSPE-PEG to retain the encapsulated Ce6 and prevent serum protein adsorption and macrophage recognition that hinder tumor targeting. Finally, the coat is conjugated to the acidity-triggered rational membrane (ATRAM) peptide, which promotes specific and efficient internalization into malignant cells in the mildly acidic microenvironment of tumors. The nanospheres facilitated tumor magnetic resonance and thermal and fluorescence imaging and exhibited potent NIR laser light-induced anticancer effects and via combined ROS production and localized hyperthermia, with negligible toxicity to healthy tissue, hence markedly extending survival. Our results demonstrate that the ATRAM-functionalized, lipid/PEG-coated upconversion mesoporous silica nanospheres (ALUMSNs) offer multimodal diagnostic imaging and targeted combinatorial cancer therapy.
PubMed: 37702397
DOI: 10.1021/acsnano.3c04564 -
Indian Journal of Critical Care... Nov 2023: Accamma K, Shamarao S, Ram A, Devananda NS, Krishna M, Bandagi LS, . Severe Diabetic Ketoacidosis with Malignant Hyperthermia Like Syndrome and Rhabdomyolysis Treated...
: Accamma K, Shamarao S, Ram A, Devananda NS, Krishna M, Bandagi LS, . Severe Diabetic Ketoacidosis with Malignant Hyperthermia Like Syndrome and Rhabdomyolysis Treated with ECMO: Unusual Severity and a Rare Occurrence. Indian J Crit Care Med 2023;27(11):859-860.
PubMed: 37936798
DOI: 10.5005/jp-journals-10071-24569 -
BMC Medical Informatics and Decision... Sep 2023Malignant hyperthermia (MH) is a rare anesthetic emergency with a high mortality rate in China. We developed a WeChat applet-based National Remote Emergency System for...
BACKGROUND
Malignant hyperthermia (MH) is a rare anesthetic emergency with a high mortality rate in China. We developed a WeChat applet-based National Remote Emergency System for Malignant Hyperthermia (MH-NRES) to provide a real-time emergency system to help Chinese anesthesiologists deal with MH crises. However, it is imperative that close attention should be paid to the usability of the applet.
PURPOSE
The objectives of this study were to (1) evaluate the usability of the applet-based MH-NRES for anesthesiologists; and (2) to test the validity and reliability of a modified mHealth app usability questionnaire.
METHODS
A modified User Version of the Mobile Application Rating Scale (uMARS) was designed. Together with System Usability Scale (SUS) and Post-Study System Usability Questionnaire (PSSUQ), another two well-validated questionnaires, uMARS were then used to evaluate the usability of MH-NRES. The Cronbach alpha of the total score and the subscales of uMARS was calculated to evaluate the internal consistency. The correlation coefficients among three questionnaires were calculated.
RESULTS
In this study, 118 anesthesiologists provided responses to the questionnaire. The overall mean uMARS score was 4.43 ± 0.61, which ranged from 3 to 5. The mean PSSUQ score were in good to excellent range with mean of 6.02 ± 0.97, which ranged from 3.19 to 7. The overall SUS score was 76.0 ± 17.6, which ranged from 45 to 100. The total uMARS score had excellent internal consistency (Cronbach alpha = 0.984). uMARS and its subscales were strongly correlated with PSSUQ (coefficient 0.758-0.819, P < 0.001) and SUS (coefficient 0.535-0.561, P < 0.001), respectively.
CONCLUSIONS
Data obtained from the usability evaluation questionnaires in this study indicated a high quality of the MH-NRES on the ease of use, satisfaction and perceived usefulness, which suggest this system might be a useful tool for anesthesiologists' education and management of MH crises. Future feedback from high-fidelity simulation and clinical scenarios are need for further usability evaluation of this system.
Topics: Humans; Malignant Hyperthermia; Reproducibility of Results; Mobile Applications; China; Computer Simulation
PubMed: 37670310
DOI: 10.1186/s12911-023-02275-4 -
Veterinarni Medicina Nov 2023Malignant hyperthermia (MH) is a clinical syndrome exhibiting elevation of expired carbon dioxide, hyperthermia, muscle rigidity, rhabdomyolysis, acidosis and...
Malignant hyperthermia (MH) is a clinical syndrome exhibiting elevation of expired carbon dioxide, hyperthermia, muscle rigidity, rhabdomyolysis, acidosis and hyperkalaemia, as well as cardiac dysrhythmia and renal failure. The syndrome manifests itself as a response to anaesthetic agents, such as e.g., halothane, desflurane, and succinylcholine. Depending on the animal species, MH is characterised by autosomal dominant or recessive inheritance, and so far two genes have been identified whose mutations can be linked to MH: and . In different species, various mutations of the gene have been described which may underlie MH. One of these mutations in dogs is T1640C, which results in the substitution of alanine for valine of the amino acid 547 (V547A) in the RYR1 protein. In our work, we aimed to investigate MH at the DNA level by identifying the T1640C mutation in a group of 50 dogs. For this purpose we used the PCR-RFLP technique, and in six dogs also direct sequencing of PCR products and subsequent comparison of their sequences with the RYR1 gene sequence in an online database. The results of our study show that none of the dogs analysed had any mutant allele of the RYR1 gene, indicating that none should be affected by MH.
PubMed: 38163044
DOI: 10.17221/46/2023-VETMED -
Heliyon Apr 2024Radiofrequency ablation (RFA) is an effective alternative to surgery for managing some malignant solid tumors. However, for medium-to-large tumors (>3 cm), tumors... (Review)
Review
Radiofrequency ablation (RFA) is an effective alternative to surgery for managing some malignant solid tumors. However, for medium-to-large tumors (>3 cm), tumors adjacent to large blood vessels, and certain irregular tumors, sublethal radiofrequency hyperthermia (RFH) often produces a margin of ablated tumor owing to the "heat-sink" effect. This effect typically leaves behind viable residual tumors at the margin. Several studies have reported that a sublethal RFH can significantly enhance the efficacy of chemotherapy, radiotherapy, immunotherapy, and gene therapy for malignant solid tumors. The possible mechanisms by which RFH enhances these therapies include heat-induced tissue fracturing, increased permeability of the cytoplasmic membrane, exaggerated cellular metabolism, blockade of the repair pathways of radiation-damaged tumor cells, and activation of the heat shock protein pathways. Therefore, RFA in combination with chemotherapy, radiotherapy, immunotherapy, or gene therapy may help reduce the rates of residual and recurrent tumors after RFA of malignant solid tumors.
PubMed: 38681568
DOI: 10.1016/j.heliyon.2024.e29866 -
Scientific Reports Jul 2023Peritoneal mesothelioma (PM) is a rare malignancy with poor prognosis, representing about 10-15% of all mesothelioma cases. Herein we apply PM patient-derived tumor...
Peritoneal mesothelioma (PM) is a rare malignancy with poor prognosis, representing about 10-15% of all mesothelioma cases. Herein we apply PM patient-derived tumor organoids (PTOs) in elucidating personalized HIPEC responses to bypass rarity of disease in generating preclinical data. Specimens were obtained from PM patients undergoing cytoreductive surgery with HIPEC. PTOs were fabricated with tumor cells suspended in ECM-hydrogel and treated with HIPEC regimen parameters. Viability and characterization analyses were performed post-treatment. Treatment efficacy was defined as ≥ 50% viability reduction and p < 0.05 compared to controls. From October 2020 to November 2022, 17 tumors from 7 patients were biofabricated into organoids, with 16/17 (94.1%) sites undergoing comparative 37° and 42° treatments with cisplatin and mitomycin C (MMC). Hyperthermic cisplatin and MMC enhanced cytotoxicity which reduced treatment viability by 25% and 22%, respectively, compared to normothermia. Heated cisplatin displayed the greatest cytotoxicity, with efficacy in 12/16 (75%) tumors and an average viability of 38% (5-68%). Heated MMC demonstrated efficacy in 7/16 (43.8%) tumors with an average treatment viability of 51% (17-92.3%). PTOs fabricated from distinct anatomic sites exhibited site-specific variability in treatment responses. PM PTOs exhibit patient and anatomic location treatment responses suggestive of underlying disease clonality. In PM organoids cisplatin is superior to MMC in HIPEC.
Topics: Humans; Mitomycin; Cisplatin; Hyperthermic Intraperitoneal Chemotherapy; Combined Modality Therapy; Hyperthermia, Induced; Mesothelioma; Mesothelioma, Malignant; Peritoneal Neoplasms; Perfusion; Organoids; Antineoplastic Combined Chemotherapy Protocols; Retrospective Studies
PubMed: 37468581
DOI: 10.1038/s41598-023-38545-4 -
Journal of Nanobiotechnology Mar 2024Breast cancer ranks first among malignant tumors, of which triple-negative breast cancer (TNBC) is characterized by its highly invasive behavior and the worst prognosis....
BACKGROUND
Breast cancer ranks first among malignant tumors, of which triple-negative breast cancer (TNBC) is characterized by its highly invasive behavior and the worst prognosis. Timely diagnosis and precise treatment of TNBC are substantially challenging. Abnormal tumor vessels play a crucial role in TNBC progression and treatment. Nitric oxide (NO) regulates angiogenesis and maintains vascular homeostasis, while effective NO delivery can normalize the tumor vasculature. Accordingly, we have proposed here a tumor vascular microenvironment remodeling strategy based on NO-induced vessel normalization and extracellular matrix collagen degradation with multimodality imaging-guided nanoparticles against TNBC called DNMF/PLGA.
RESULTS
Nanoparticles were synthesized using a chemotherapeutic agent doxorubicin (DOX), a NO donor L-arginine (L-Arg), ultrasmall spinel ferrites (MnFeO), and a poly (lactic-co-glycolic acid) (PLGA) shell. Nanoparticle distribution in the tumor was accurately monitored in real-time through highly enhanced magnetic resonance imaging and photoacoustic imaging. Near-infrared irradiation of tumor cells revealed that MnFeO catalyzes the production of a large amount of reactive oxygen species (ROS) from HO, resulting in a cascade catalysis of L-Arg to trigger NO production in the presence of ROS. In addition, DOX activates niacinamide adenine dinucleotide phosphate oxidase to generate and supply HO. The generated NO improves the vascular endothelial cell integrity and pericellular contractility to promote vessel normalization and induces the activation of endogenous matrix metalloproteinases (mainly MMP-1 and MMP-2) so as to promote extravascular collagen degradation, thereby providing an auxiliary mechanism for efficient nanoparticle delivery and DOX penetration. Moreover, the chemotherapeutic effect of DOX and the photothermal effect of MnFeO served as a chemo-hyperthermia synergistic therapy against TNBC.
CONCLUSION
The two therapeutic mechanisms, along with an auxiliary mechanism, were perfectly combined to enhance the therapeutic effects. Briefly, multimodality image-guided nanoparticles provide a reliable strategy for the potential application in the fight against TNBC.
Topics: Humans; Nitric Oxide; Triple Negative Breast Neoplasms; Reactive Oxygen Species; Hydrogen Peroxide; Doxorubicin; Hyperthermia, Induced; Nanoparticles; Phototherapy; Collagen; Cell Line, Tumor; Tumor Microenvironment
PubMed: 38481281
DOI: 10.1186/s12951-024-02366-y -
International Journal of Molecular... Mar 2024Malignant hyperthermia (MH) is a pharmacogenetic condition of skeletal muscle that manifests in hypermetabolic responses upon exposure to volatile anaesthetics. This...
Malignant hyperthermia (MH) is a pharmacogenetic condition of skeletal muscle that manifests in hypermetabolic responses upon exposure to volatile anaesthetics. This condition is caused primarily by pathogenic variants in the calcium-release channel RYR1, which disrupts calcium signalling in skeletal muscle. However, our understanding of MH genetics is incomplete, with no variant identified in a significant number of cases and considerable phenotype diversity. In this study, we applied a transcriptomic approach to investigate the genome-wide gene expression in MH-susceptible cases using muscle biopsies taken for diagnostic testing. Baseline comparisons between muscle from MH-susceptible individuals (MHS, = 8) and non-susceptible controls (MHN, = 4) identified 822 differentially expressed genes (203 upregulated and 619 downregulated) with significant enrichment in genes associated with oxidative phosphorylation (OXPHOS) and fatty acid metabolism. Investigations of 10 OXPHOS target genes in a larger cohort (MHN: = 36; MHS: = 36) validated the reduced expression of and in MHS samples, but the remaining 8 selected were not statistically significant. Further analysis also identified evidence of a sex-linked effect in and expression, and a difference in expression across individuals with MH sub-phenotypes (trigger from in vitro halothane exposure only, MHS ( = 4); trigger to both in vitro halothane and caffeine exposure, MHS ( = 4)). Our data support a link between MH-susceptibility and dysregulated gene expression associated with mitochondrial bioenergetics, which we speculate plays a role in the phenotypic variability observed within MH.
Topics: Humans; Malignant Hyperthermia; Halothane; Oxidative Phosphorylation; Calcium; Muscle, Skeletal; Disease Susceptibility; Biopsy; Gene Expression; Muscle Contraction; Ryanodine Receptor Calcium Release Channel; Carrier Proteins
PubMed: 38542460
DOI: 10.3390/ijms25063489