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Journal of Pediatric Genetics Dec 2023Congenital myopathies are an expanding spectrum of neuromuscular disorders with early infantile or childhood onset hypotonia and slowly or nonprogressive skeletal muscle...
Congenital myopathies are an expanding spectrum of neuromuscular disorders with early infantile or childhood onset hypotonia and slowly or nonprogressive skeletal muscle weakness. -related myopathies are the most common and frequently diagnosed class of congenital myopathies. Malignant hyperthermia susceptibility and central core disease are autosomal dominant or de novo disorder, whereas multiminicore, congenital fiber type disproportion and centronuclear myopathy are autosomal recessive disorders. The presence of ptosis, ophthalmoparesis, facial, and proximal muscles weakness, with the presence of dusty cores and multiple internal nuclei on muscle biopsy are clues to the diagnosis. We describe an 18-year-old male, who presented with early infantile onset ptosis, ophthalmoplegia, myopathic facies, hanging lower jaw, and proximal muscle weakness confirmed as an -related congenital centronuclear myopathy on genetic analysis and muscle biopsy.
PubMed: 38162159
DOI: 10.1055/s-0041-1731683 -
European Journal of Anaesthesiology May 2024Delays in treating anaesthesia-induced malignant hyperthermia increase risks of complications and death. NPJ5008 is a novel formulation of the indicated treatment,... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Delays in treating anaesthesia-induced malignant hyperthermia increase risks of complications and death. NPJ5008 is a novel formulation of the indicated treatment, dantrolene sodium, developed to shorten preparation and administration times compared with the reference formulation Dantrium®. The two formulations have been compared preclinically.
OBJECTIVES
Assess bioequivalence of overall dantrolene (free acid) exposure of NPJ5008 versus Dantrium® and ascertain similarities in their pharmacokinetics and safety/tolerability profiles. Evaluate preparation/administration time savings for the new formulation.
DESIGN
Part 1 of this open-label trial in humans was a 1 : 1 randomised crossover study; part 2 was a single-arm study. Trial pharmacy data and laboratory simulations assessed preparation/administration step timings.
SETTING
Single clinical centre in the UK, April to July 2021.
PARTICIPANTS
Twenty-one healthy male and female individuals.
INTERVENTIONS
Part 1: single intravenous 60 mg dose of NPJ5008 or Dantrium®, sequentially. Part 2: single intravenous 120 mg dose of NPJ5008. Simulation: five vials per formulation using paediatric and adult cannulas.
MAIN OUTCOME MEASURES
Overall drug exposure to last measurable concentration (AUC 0 to last ) and extrapolated to infinity (AUC 0 to ∞ ) were primary endpoints. Other pharmacokinetic, clinical and muscle-function parameters, and adverse events, were monitored.
RESULTS
Adjusted geometric mean ratios of NPJ5008 versus Dantrium® were 90.24 and 90.44% for AUC 0 to last and AUC 0 to ∞ , respectively, with the 90% confidence intervals (CI) within the 80 to 125% acceptance interval, establishing bioequivalence. No new safety issues emerged: any adverse events were of a similar magnitude across treatments and related to pharmacological properties of dantrolene. Pharmacy and simulation data revealed that every step in preparation and administration was 26 to 69% faster for NPJ5008 than Dantrium®.
CONCLUSION
NPJ5008 showed comparable pharmacokinetic and safety profiles to Dantrium®, while reducing dantrolene dose preparation/administration times, potentially reducing patient complications/healthcare resourcing in malignant hyperthermia.
TRIAL REGISTRATION
EudraCT Number: 2020-005719-35, MHRA approval.
Topics: Adult; Humans; Male; Female; Child; Dantrolene; Biological Availability; Malignant Hyperthermia; Healthy Volunteers; Therapeutic Equivalency; Cross-Over Studies; Area Under Curve; Administration, Oral
PubMed: 38445365
DOI: 10.1097/EJA.0000000000001966 -
International Journal of Hyperthermia :... 2024A meta-analysis was conducted to assess the efficacy and safety of cryoablation (CRA) compared with radiofrequency ablation (RFA). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
A meta-analysis was conducted to assess the efficacy and safety of cryoablation (CRA) compared with radiofrequency ablation (RFA).
METHODS
A systematic search of PubMed, EMBASE, Cochrane Library, Wanfang, CNKI, and VIP databases was conducted to identify clinical controlled studies comparing CRA versus RFA for hepatic malignancies up to July 2022. The meta-analysis was performed using RevMan 5.3.
RESULTS
A comprehensive analysis was conducted on 8 clinical controlled studies involving a total of 943 patients. There were no significant differences in the incidence of complications, complete ablation of lesions, local recurrence, and 1-year survival between the CRA and RFA groups (OR = 0.98, 95%CI: 0.61-1.55, = 0.92; OR = 1.08, 95%CI: 0.62-1.90, = 0.78; OR = 1.28, 95%CI: 0.49-3.36, = 0.61; and OR = 1.14, 95%CI: 0.63-2.06, = 0.66, respectively).
CONCLUSION
The efficacy and safety profile of CRA was comparable to that of RFA in the context of ablation therapy for hepatic malignancies. These findings suggested that CRA may be a valuable alternative to RFA in the treatment of hepatic malignancies.
Topics: Humans; Carcinoma, Hepatocellular; Cryosurgery; Liver Neoplasms; Radiofrequency Ablation
PubMed: 38190758
DOI: 10.1080/02656736.2023.2300347 -
Scientific Reports Jul 2023Initially diagnosed malignant pleural effusion (MPE) has different systematic treatments, and defining the best drainage regimen according to the responsiveness of MPE...
Initially diagnosed malignant pleural effusion (MPE) has different systematic treatments, and defining the best drainage regimen according to the responsiveness of MPE to different systematic treatments is important. This study compared the efficacy of hyperthermic intrathoracic chemotherapy (HITHOC) and pleural catheter drainage (IPCD) for initially diagnosed lung cancer with symptomatic MPE. We retrospectively reviewed the medical records of initially diagnosed lung cancer patients with symptomatic MPE between January 2018 and May 2022. The patients were treated with IPCD or HITHOC for local control of MPE after diagnosis. Systematic regimens were conducted during 1 month according to guidelines after local treatment. Intrathoracic MPE progression-free survival (iPFS) and overall survival (OS) were calculated, Univariate and multivariable Cox-regression were used to identify factors associated with iPFS and OS. A total of 33 patients were evaluated; 10 (30.3%) patients received IPCD, and 23 (69.7%) patients received HITHOC. No difference in the MPE control rate at 1 month was found between the IPCD group (90%) and HITHOC group (95.7%). However, this control rate was significantly higher in the HITHOC group (69.6%) than in the IPCD group (30%) at 3 months (P = 0.035). Multivariate analysis showed that receiving tyrosine kinase inhibitors (TKIs) or chemotherapy was a significant protective factor for iPFS (HR = 0.376, 95% CI 0.214-0.659, P = 0.007) and OS (HR = 0.321, 95% CI 0.174-0.594, P < 0.001). According to subgroup analysis, among patients treated with TKIs, those who received HITHOC had longer iPFS and OS than those who received IPCD (P = 0.011 and P = 0.002, respectively), but this difference was not found in the palliative care subgroup. Moreover, no patients treated with chemotherapy showed reaccumulation of MPE. Systematic TKIs or chemotherapy prolonged iPFS and OS for those initially diagnosed with lung cancer with symptomatic MPE. HITHOC prolonged iPFS and OS for those treated with systematic TKIs.
Topics: Humans; Pleural Effusion, Malignant; Retrospective Studies; Lung Neoplasms; Hyperthermia, Induced
PubMed: 37495659
DOI: 10.1038/s41598-023-39211-5 -
JMIR Perioperative Medicine Nov 2023More than 300 million patients undergo surgical procedures requiring anesthesia worldwide annually. There are 2 standard-of-care general anesthesia administration...
Description of the Content and Quality of Publicly Available Information on the Internet About Inhaled Volatile Anesthesia and Total Intravenous Anesthesia: Descriptive Study.
BACKGROUND
More than 300 million patients undergo surgical procedures requiring anesthesia worldwide annually. There are 2 standard-of-care general anesthesia administration options: inhaled volatile anesthesia (INVA) and total intravenous anesthesia (TIVA). There is limited evidence comparing these methods and their impact on patient experiences and outcomes. Patients often seek this information from sources such as the internet. However, the majority of websites on anesthesia-related topics are not comprehensive, updated, and fully accurate. The quality and availability of web-based patient information about INVA and TIVA have not been sufficiently examined.
OBJECTIVE
This study aimed to (1) assess information on the internet about INVA and TIVA for availability, readability, accuracy, and quality and (2) identify high-quality websites that can be recommended to patients to assist in their anesthesia information-seeking and decision-making.
METHODS
Web-based searches were conducted using Google from April 2022 to November 2022. Websites were coded using a coding instrument developed based on the International Patient Decision Aids Standards criteria and adapted to be appropriate for assessing websites describing INVA and TIVA. Readability was calculated with the Flesch-Kincaid (F-K) grade level and the simple measure of Gobbledygook (SMOG) readability formula.
RESULTS
A total of 67 websites containing 201 individual web pages were included for coding and analysis. Most of the websites provided a basic definition of general anesthesia (unconsciousness, n=57, 85%; analgesia, n=47, 70%). Around half of the websites described common side effects of general anesthesia, while fewer described the rare but serious adverse events, such as intraoperative awareness (n=31, 46%), allergic reactions or anaphylaxis (n=29, 43%), and malignant hyperthermia (n=18, 27%). Of the 67 websites, the median F-K grade level was 11.3 (IQR 9.5-12.8) and the median SMOG score was 13.5 (IQR 12.2-14.4), both far above the American Medical Association (AMA) recommended reading level of sixth grade. A total of 51 (76%) websites distinguished INVA versus TIVA as general anesthesia options. A total of 12 of the 51 (24%) websites explicitly stated that there is a decision to be considered about receiving INVA versus TIVA for general anesthesia. Only 10 (20%) websites made any direct comparisons between INVA and TIVA, discussing their positive and negative features. A total of 12 (24%) websites addressed the concept of shared decision-making in planning anesthesia care, but none specifically asked patients to think about which features of INVA and TIVA matter the most to them.
CONCLUSIONS
While the majority of websites described INVA and TIVA, few provided comparisons. There is a need for high-quality patient education and decision support about the choice of INVA versus TIVA to provide accurate and more comprehensive information in a format conducive to patient understanding.
PubMed: 37917148
DOI: 10.2196/47714 -
International Journal of Nanomedicine 2024This study aimed to construct targeting drug-loading nanocomposites (FA-FePt/DDP nanoliposomes) to explore their potential in ovarian cancer therapy and molecular...
PURPOSE
This study aimed to construct targeting drug-loading nanocomposites (FA-FePt/DDP nanoliposomes) to explore their potential in ovarian cancer therapy and molecular magnetic resonance imaging (MMRI).
METHODS
FA-FePt-NPs were prepared by coupling folate (FA) with polyethylene-glycol (PEG)-coated ferroplatinum nanoparticles and characterized. Then cisplatin (DDP) was encapsulated in FA-FePt-NPs to synthesize FA-PEG-FePt/DDP nanoliposomes by thin film-ultrasonic method and high-speed stirring, of which MMRI potential, magnetothermal effect, and the other involved performance were analyzed. The therapeutic effect of FA-FePt/DDP nanoliposomes combined with magnetic fluid hyperthermia (MFH) on ovarian cancer in vitro and in vivo was evaluated. The expression levels of Bax and epithelial-mesenchymal transition related proteins were detected. The biosafety was also preliminarily observed.
RESULTS
The average diameter of FA-FePt-NPs was about 30 nm, FA-FePt/DDP nanoliposomes were about 70 nm in hydrated particle size, with drug slow-release and good cell-specific targeted uptake. In an alternating magnetic field (AMF), FA-FePt/DDP nanoliposomes could rapidly reach the ideal tumor hyperthermia temperature (42~44 °C). MRI scan showed that FA-FePt-NPs and FA-FePt/DDP nanoliposomes both could suppress the T2 signal, indicating a good potential for MMRI. The in vitro and in vivo experiments showed that FA-FePt/DDP-NPs in AMF could effectively inhibit the growth of ovarian cancer by inhibiting cancer cell proliferation, invasion, and migration, and inducing cancer cell apoptosis, much better than that of the other individual therapies; molecularly, E-cadherin and Bax proteins in ovarian cancer cells and tissues were significantly increased, while N-cadherin, Vimentin, and Bcl-2 proteins were inhibited, effectively inhibiting the malignant progression of ovarian cancer. In addition, no significant pathological injury and dysfunction was observed in major visceras.
CONCLUSION
We successfully synthesized FA-FePt/DDP nanoliposomes and confirmed their good thermochemotherapeutic effect in AMF and MMRI potential on ovarian cancer, with no obvious side effects, providing a favorable strategy of integrated targeting therapy and diagnosis for ovarian cancer.
Topics: Female; Ovarian Neoplasms; Liposomes; Cisplatin; Animals; Folic Acid; Humans; Magnetic Resonance Imaging; Polyethylene Glycols; Cell Line, Tumor; Antineoplastic Agents; Mice; Platinum; Hyperthermia, Induced; Nanocomposites; Mice, Nude; Mice, Inbred BALB C; Metal Nanoparticles; Magnetic Fields; Particle Size
PubMed: 38855734
DOI: 10.2147/IJN.S453601 -
Beilstein Journal of Nanotechnology 2024Hepatocellular carcinoma (HCC) is the sixth most common malignant tumor and the third leading cause of cancer death worldwide. Most patients are diagnosed at an advanced...
Hepatocellular carcinoma (HCC) is the sixth most common malignant tumor and the third leading cause of cancer death worldwide. Most patients are diagnosed at an advanced stage, and systemic chemotherapy is the preferred treatment modality for advanced HCC. Curcumin (CUR) is a polyphenolic antineoplastic drug with low toxicity obtained from plants. However, its low bioavailability and poor solubility limit its functionality. In this study, radiofrequency- (RF) enhanced responsive nanoflowers (NFs), containing superparamagnetic ferric oxide nanoclusters (FeO NCs), - CUR layer, - and MnO (CUR-Fe@MnO NFs), were verified to have a thermal therapeutic effect. Transmission electron microscopy was used to characterize the CUR-Fe@MnO NFs, which appeared flower-like with a size of 96.27 nm. The in vitro experimental data showed that RF enhanced the degradation of CUR-Fe@MnO NFs to release Mn and CUR. The cytotoxicity test results indicated that after RF heating, the CUR-Fe@MnO NFs significantly suppressed HCC cell proliferation. Moreover, CUR-Fe@MnO NFs were effective / contrast agents for molecular magnetic resonance imaging due to the release of Mn and FeO NCs.
PubMed: 38887527
DOI: 10.3762/bjnano.15.49 -
Qatar Medical Journal 2023Parkinsonism-hyperpyrexia syndrome (PHS) is a potentially life-threatening condition that occurs due to the abrupt withdrawal or significant dose reduction of...
BACKGROUND
Parkinsonism-hyperpyrexia syndrome (PHS) is a potentially life-threatening condition that occurs due to the abrupt withdrawal or significant dose reduction of antiparkinsonian medications. It presents similarly to neuroleptic malignant syndrome (NMS) and is characterized by severe rigidity, fever, autonomic instability, and altered mental status.
CASE
A 62-year-old male with a 10-year history of Parkinson's disease (PD) underwent laparoscopic mesh repair for a left-sided diaphragmatic and large hiatus hernia. His antiparkinsonian medications included levodopa/carbidopa, amantadine, pramipexole, and benzhexol. Medications were withheld as part of the nil per os (NPO) status. Postoperatively, he developed withdrawal features, including tremors, difficulty speaking, tachycardia, hypertension, fever, and sweating. PHS, resulting from the withdrawal of antiparkinsonian medications, was diagnosed. The patient was transferred to the intensive care unit (ICU), intubated, and his antiparkinsonian medications were reintroduced. The patient's condition improved gradually, and he was discharged home on the 15th postoperative day.
DISCUSSION
The abrupt discontinuation of antiparkinsonian medications precipitated PHS in our patient. Recognizing the clinical picture of PHS and differentiating it from other possible conditions, such as neuroleptic malignant syndrome and malignant hyperthermia, is pivotal. Management involves resuming medications and providing supportive care. Early recognition and prompt reintroduction of the antiparkinsonian medications are essential for the patient's recovery.
CONCLUSION
PHS is a rare but potentially life-threatening condition that occurs due to the withdrawal of antiparkinsonian medications, leading to an acute hypodopaminergic state. Our case emphasizes the importance of careful perioperative management of antiparkinsonian medications and early recognition and management of withdrawal symptoms in patients with Parkinson's disease undergoing surgery.
PubMed: 38204562
DOI: 10.5339/qmj.2023.34 -
Brazilian Journal of Anesthesiology... 2024
Topics: Humans; Malignant Hyperthermia; Disease Susceptibility; Halothane
PubMed: 37820766
DOI: 10.1016/j.bjane.2023.10.001 -
BMC Psychiatry Jun 2024Malignant hyperthermia is a potentially lethal condition triggered by specific anesthetic drugs, especially a depolarizing muscle relaxant of succinylcholine...
BACKGROUND
Malignant hyperthermia is a potentially lethal condition triggered by specific anesthetic drugs, especially a depolarizing muscle relaxant of succinylcholine (Suxamethonium). Despite the frequent use of succinylcholine with electroconvulsive therapy (ECT), there has been no reported case of potentially lethal malignant hyperthermia following ECT. In addition, the time interval between the administration of succinylcholine and the onset of malignant hyperthermia has not been outlined in the context of ECT.
CASE PRESENTATION
We present the case of a 79-year-old woman suffering from severe depression, who experienced severe malignant hyperthermia due to succinylcholine administration during an ECT session. She presented with a high fever of 40.2 °C, tachycardia of 140/min, hypertension with a blood pressure exceeding 200 mmHg, significant muscle rigidity, and impaired consciousness. These symptoms emerged two hours after ECT, which occurred in a psychiatric ward rather than an operating room, and reached their peak in less than 24 h. She was given 60 mg of dantrolene, which quickly reduced the muscular rigidity. Subsequently, she received two additional doses of 20 mg and 60 mg of dantrolene, which brought her fever down to 36.2 °C and completely eased her muscle rigidity within two days after ECT.
CONCLUSIONS
This is the first reported case of potentially lethal malignant hyperthermia after ECT. In addition, it highlights the delayed onset of malignant hyperthermia following an ECT procedure, emphasizing the necessity for psychiatrists to recognize its onset even after the treatment. In the light of potentially lethal consequences of malignant hyperthermia, it is critically important for psychiatrists to closely monitor both intraoperative and postoperative patient's vital signs and characteristic physical presentations, promptly identify any symptomatic emergence, and treat it immediately with dantrolene.
Topics: Humans; Succinylcholine; Electroconvulsive Therapy; Aged; Malignant Hyperthermia; Female; Neuromuscular Depolarizing Agents; Dantrolene; Psychiatrists
PubMed: 38834964
DOI: 10.1186/s12888-024-05846-5