-
Asian Journal of Surgery Aug 2023
PubMed: 37625965
DOI: 10.1016/j.asjsur.2023.08.016 -
Genes Oct 2023Remimazolam is a novel general anesthetic and its safety in patients with malignant hyperthermia (MH) is unknown. We used myotubes derived from the skeletal muscle of...
Effects of Remimazolam on Intracellular Calcium Dynamics in Myotubes Derived from Patients with Malignant Hyperthermia and Functional Analysis of Type 1 Ryanodine Receptor Gene Variants.
Remimazolam is a novel general anesthetic and its safety in patients with malignant hyperthermia (MH) is unknown. We used myotubes derived from the skeletal muscle of patients with MH to examine the response to ryanodine receptor 1 (RYR1) agonist and remimazolam in MH-susceptible patients. Patients underwent muscle biopsy for the Ca-induced Ca release (CICR) rate test, a diagnostic tool for MH in Japan. Ten patients had myotubes obtained from skeletal muscle cultures, and the genes associated with malignant hyperthermia in these patients were analyzed. The EC of caffeine, cresol, and remimazolam to induce intracellular calcium concentration change were compared between myotubes from CICR-negative genetic test patients and myotubes from other patients. Eight of the ten were CICR-positive, five of whom had RYR1 causative gene mutations or variants. Two patients had CICR-negative genetic tests, and as expected had the highest EC (the concentration of a drug that gives a half-maximal response) in response to caffeine, 4CmC and remimazolam. Three patients had a positive CICR but no known variants in RYR1 or CACNA1S (voltage-gated calcium channel subunit alpha1S). Myotubes in these patients had significantly lower EC50s for all agents than myotubes in CICR-negative patients. When myotubes from a patient who was CICR-negative and had no gene variant were used as a control, myotubes from CICR-positive patients were more hyper-responsive than controls to all stimulants used. The EC for remimazolam was lowest for myotubes from CICR-positive, RYR1-mutant patients, at 206 µM (corresponding to 123 µg/mL). The concentration was more than 80-times higher than the clinical concentration. gene variants in R4645Q and W5020G were shown to be causative gene mutations for MH. Intracellular calcium in myotubes from MH patients are elevated at high concentrations of remimazolam but not at clinically used concentrations of remimazolam. Remimazolam appears to be safe to use in patients with MH.
Topics: Humans; Ryanodine Receptor Calcium Release Channel; Malignant Hyperthermia; Calcium; Caffeine; Muscle Fibers, Skeletal
PubMed: 38002952
DOI: 10.3390/genes14112009 -
Environmental Research Sep 2023The multidisciplinary approaches in treatment of cancer appear to be essential in term of bringing benefits of several disciplines and their coordination in tumor... (Review)
Review
The multidisciplinary approaches in treatment of cancer appear to be essential in term of bringing benefits of several disciplines and their coordination in tumor elimination. Because of the biological and malignant features of cancer cells, they have ability of developing resistance to conventional therapies such as chemo- and radio-therapy. Pancreatic cancer (PC) is a malignant disease of gastrointestinal tract in which chemotherapy and radiotherapy are main tools in its treatment, and recently, nanocarriers have been emerged as promising structures in its therapy. The bioresponsive nanocarriers are able to respond to pH and redox, among others, in targeted delivery of cargo for specific treatment of PC. The loading drugs on the nanoparticles that can be synthetic or natural compounds, can help in more reduction in progression of PC through enhancing their intracellular accumulation in cancer cells. The encapsulation of genes in the nanoparticles can protect against degradation and promotes intracellular accumulation in tumor suppression. A new kind of therapy for cancer is phototherapy in which nanoparticles can stimulate both photothermal therapy and photodynamic therapy through hyperthermia and ROS overgeneration to trigger cell death in PC. Therefore, synergistic therapy of phototherapy with chemotherapy is performed in accelerating tumor suppression. One of the important functions of nanotechnology is selective targeting of PC cells in reducing side effects on normal cells. The nanostructures are capable of being surface functionalized with aptamers, proteins and antibodies to specifically target PC cells in suppressing their progression. Therefore, a specific therapy for PC is provided and future implications for diagnosis of PC is suggested.
Topics: Humans; Multifunctional Nanoparticles; Doxorubicin; Hyperthermia, Induced; Phototherapy; Neoplasms; Nanoparticles; Pancreatic Neoplasms; Cell Line, Tumor
PubMed: 37354932
DOI: 10.1016/j.envres.2023.116490 -
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 -
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 -
Journal of Surgical Oncology Sep 2023Pleural metastasis has extremely poor prognosis. Resection of pleural implants with infusion of intrathoracic hyperthermic chemotherapy may offer a survival advantage in... (Review)
Review
OBJECTIVES
Pleural metastasis has extremely poor prognosis. Resection of pleural implants with infusion of intrathoracic hyperthermic chemotherapy may offer a survival advantage in selected patients. We evaluated the safety and efficacy of hyperthermic intrathoracic extracorporeal chemotherapy (HITEC) in patients who underwent pleurectomy/decortication (P/D) for secondary malignant pleural disease (SPD).
METHODS
A total of 101 patients were evaluated over 72 months, with 35 patients electing to proceed with P/D and 60 minutes of HITEC with cisplatin at 42°C. Inclusion criteria were adults 18-79 years with unilateral pleural dissemination. Exclusion criteria were patients without control of primary site, extrathoracic metastatic disease, significant comorbidities, and a history of adverse reaction to cisplatin.
RESULTS
Median age was 56 years (36-73); 60% were women. SPD was thymoma in 13, breast cancer in 9, lung cancer in 6, colon cancer in 2, renal cell in 2, and esophageal, anal, and thymic cancers in one each. There was no operative mortality. Postoperative complications occurred in 18 patients (51%). No patient developed renal failure. Median follow-up was 24 months (4-60). The overall survival rate was 61%; 17 patients (49%) developed recurrent disease at a median of 12 months (6-36). There were no recurrences after 36 months Eleven patients (31%) died of metastatic disease at a median of 17 months (7-25).
CONCLUSIONS
Surgical cytoreduction of SPD followed by HITEC with cisplatin was well tolerated. No patient developed cisplatin-related toxicities. Long-term follow-up is warranted to determine survival advantage and refinement of inclusion criteria.
Topics: Adult; Humans; Female; Middle Aged; Male; Cisplatin; Combined Modality Therapy; Pleural Neoplasms; Mesothelioma; Thymus Neoplasms; Pleural Diseases; Hyperthermia, Induced
PubMed: 37409778
DOI: 10.1002/jso.27389 -
Nanomaterials (Basel, Switzerland) Aug 2023Magnetic nanoparticles (MNPs) with various shapes and special (magnetic and thermal) properties are promising for magnetic hyperthermia. The efficiency of this therapy...
Magnetic nanoparticles (MNPs) with various shapes and special (magnetic and thermal) properties are promising for magnetic hyperthermia. The efficiency of this therapy depends mainly on the MNPs' physical characteristics: types, sizes and shapes. This paper presents the hyperthermic temperature values induced by cubic/sphere-shaped MNPs injected within a concentric tissue configuration (malignant and healthy tissues) when an external time-dependent magnetic field was applied. The space-time distribution of the nanoparticles as a result of their injection within a tumoral (benign/malign) tissue was simulated with the bioheat transport equation (Pennes equation). A complex thermo-fluid model that considers the space-time MNP transport and its heating was developed in Comsol Multiphysics. The cubic-shaped MNPs give a larger spatial distribution of the therapeutic temperature in the tumoral volume compared to the spherical-shaped ones. MNP doses that induce the therapeutic (hyperthermic) values of the temperature (40 ÷ 45 °C) in smaller volumes from the tumoral region were analyzed. The size of these regions (covered by the hyperthermic temperature values) was computed for different magnetite cubic/sphere-shaped MNP doses. Lower doses of the cubic-shaped MNPs give the hyperthermic values of the temperature in a larger volume from the tumoral region compared with the spheric-shaped MNPs. The MNP doses were expressed as a ratio between mass concentration and the maximum clinical accepted doses. This thermo-fluid analysis is an important computational instrument that allows the computations of the MNP doses that give therapeutic temperature values within tissues.
PubMed: 37630968
DOI: 10.3390/nano13162383 -
Cureus Sep 2023Purpose The diagnosis of malignant hyperthermia susceptibility (MHS) has significant implications for the perioperative period that may persist for generations....
Purpose The diagnosis of malignant hyperthermia susceptibility (MHS) has significant implications for the perioperative period that may persist for generations. Anesthetic medication options are reduced, anesthetic workstations require preparation to reduce exposure to inhaled volatile anesthetics, and patients may be excluded from surgery at ambulatory centers. In this study, we sought to better characterize the etiology of MHS diagnoses in our health system and the downstream effects of this diagnosis on anesthetic care. Methods We retrospectively reviewed the electronic medical records of 55 patients with a documented concern for MHS who received care at University of Florida (UF) Health between 2014 and 2020. We characterized the etiology of the patient's MHS diagnosis, whether this diagnosis was supported by formal genetic or muscle contracture testing, and the details of the recorded anesthetics that were delivered to these patients. Results The 55 patients with suspected MHS were evenly split between those with a family history of malignant hyperthermia (MH) (28/55) and those with a concern for MHS in their personal medical history (27/55). Of the 28 patients with a family history of MH, 16 reported that the affected family member was a first-degree relative, and two of these 16 reported that the affected family member had undergone confirmatory muscle contracture testing. Of the 27 patients with a personal history suspicious for MHS, two had undergone confirmatory genetic testing, and two patients had anesthetic records available for review where intraoperative MH was suspected and treated with dantrolene. An additional four patients were told of a concern about MHS due to another underlying diagnosis. No patients with a personal history suspicious of MHS had undergone confirmatory muscle contracture testing. These 55 patients underwent 87 anesthetics, and exclusively non-triggering anesthetic techniques were utilized in nearly all cases. In pediatric patients, some perioperative challenges were identified, related to the avoidance of mask inhalational induction. Only six of these 87 anesthetics occurred at our ambulatory surgery centers, a proportion (6.9%) lower than that of the general surgical population at UF Health (20.0%). Conclusions Among patients suspected to be MH susceptible in our health system over a six-year period, a minority (8/55) were supported by clear records of a prior MH event, confirmatory genetic or muscle contracture testing, or an underlying diagnosis closely linked to MH. The vast majority had limited documentation supporting their MH risk but continued to be treated with non-triggering anesthetics and were less likely to have surgery at an ambulatory surgery center than our overall surgical population. Among pediatric patients, some anesthetic challenges related to delivering non-triggering anesthetics were identified. Improving the documentation of index cases of MH and increasing referrals to clinical geneticists and genetic testing may be a viable route to decreasing the proportion of suspected MHS patients with a poorly characterized risk profile.
PubMed: 37799222
DOI: 10.7759/cureus.44661 -
Journal of Nanobiotechnology Oct 2023The combination of drug delivery with immune checkpoint targeting has been extensively studied in cancer therapy. However, the clinical benefit for patients from this...
BACKGROUND
The combination of drug delivery with immune checkpoint targeting has been extensively studied in cancer therapy. However, the clinical benefit for patients from this strategy is still limited. B7 homolog 3 protein (B7-H3), also known as CD276 (B7-H3/CD276), is a promising therapeutic target for anti-cancer treatment. It is widely overexpressed on the surface of malignant cells and tumor vasculature, and its overexpression is associated with poor prognosis. Herein, we report B7H3 targeting doxorubicin (Dox)-conjugated gold nanocages (B7H3/Dox@GNCs) with pH-responsive drug release as a selective, precise, and synergistic chemotherapy-photothermal therapy agent against non-small-cell lung cancer (NSCLC).
RESULTS
In vitro, B7H3/Dox@GNCs exhibited a responsive release of Dox in the tumor acidic microenvironment. We also demonstrated enhanced intracellular uptake, induced cell cycle arrest, and increased apoptosis in B7H3 overexpressing NSCLC cells. In xenograft tumor models, B7H3/Dox@GNCs exhibited tumor tissue targeting and sustained drug release in response to the acidic environment. Wherein they synchronously destroyed B7H3 positive tumor cells, tumor-associated vasculature, and stromal fibroblasts.
CONCLUSION
This study presents a dual-compartment targeted B7H3 multifunctional gold conjugate system that can precisely control Dox exposure in a spatio-temporal manner without evident toxicity and suggests a general strategy for synergistic therapy against NSCLC.
Topics: Humans; B7 Antigens; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Doxorubicin; Drug Liberation; Gold; Hydrogen-Ion Concentration; Hyperthermia, Induced; Lung Neoplasms; Nanoparticles; Phototherapy; Photothermal Therapy; Tumor Microenvironment; Antineoplastic Agents; Animals; Mice; Xenograft Model Antitumor Assays
PubMed: 37848956
DOI: 10.1186/s12951-023-02078-9 -
Acta Anaesthesiologica Scandinavica Jul 2024Malignant hyperthermia (MH) is a rare pharmacogenetic disorder that can lead to a life-threatening reaction during general anaesthesia with triggering agents. Prompt...
BACKGROUND
Malignant hyperthermia (MH) is a rare pharmacogenetic disorder that can lead to a life-threatening reaction during general anaesthesia with triggering agents. Prompt life-saving treatment includes the immediate administration of the antidote dantrolene. This study investigated Swedish healthcare providers' awareness and adherence to guidelines and recommendations with respect to MH and whether adherence to safe MH-praxis varies with hospital care-complexity level and private versus public management form.
METHOD
Agreements and procurement specifications between all 21 Swedish County Councils and privately run surgical care providers were reviewed alongside with questionnaire-aided collection of information from 62 publicly funded health care providers (both privately and publicly run).
RESULTS
No procurement requirement specification or contract contained requirements on anaesthesia or aspects of MH. All publicly run hospitals stocked dantrolene and 28 out of 52 (54%) stocked the recommended amount. Seven out of nine (78%) of the privately run institutions stocked dantrolene, and one stocked the recommended amount. Publicly run hospitals adhered to recommendations to a greater extent than privately run institutions, both with respect to stocking of dantrolene (p = .02) and to stocking the recommended amount (p = .03).
CONCLUSIONS
Contracts between Swedish county councils and private surgical care subcontractors rarely outline expectations of standards for the safe practice of anaesthesia such as preparedness to handle a life-threatening MH reaction. Among Swedish publicly funded anaesthesia providers there is room for improvement in adherence to the EMHG guideline on dantrolene availability. Publicly run hospitals seem to have better compliance with these recommendations than privately run institutions. Raising awareness about current guidelines is important to improve safety for known and unknown MH-susceptible individuals.
Topics: Malignant Hyperthermia; Humans; Sweden; Dantrolene; Guideline Adherence; Surveys and Questionnaires; Muscle Relaxants, Central
PubMed: 38566397
DOI: 10.1111/aas.14417