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Golden nanoparticle dimers connected by conjugated molecular linkers 1,2-bis(2-pyridyl)ethylene are produced. The formation of stable dimers with 22 nm diameter nanoparticles is confirmed by transmission electron microphotography. The possibility of charge transfer through the linkers between the particles in the dimers is shown by the density functional theory calculations. In addition to localized plasmon resonance of solitary nanoparticles with a wavelength of 530 nm, the optical spectra exhibit a new intense absorption peak in the near-infrared range with a wavelength of ∼780 nm. The emergent absorption peak is attributed to the charge-transfer plasmon (CTP) mode; the spectra simulated within the CTP developed model agree with the experimental ones. This resonant absorption may be of interest to biomedical applications due to its position in the so-called transmission window of biological tissues. The in vitro heating of CTP dimer solution by a laser diode with a wavelength of 792 nm proved the efficiency of CTP dimers for achieving a temperature increase of ΔT = 6 °C, which is sufficient for hyperthermia treatment of malignant tumors. This indicates the possibility of using hyperthermia to treat malignant tumors using the material we synthesized. [ABSTRACT FROM AUTHOR]

BACKGROUNDFXLEARN, the first-ever large multisite trial of effects of disease-targeted pharmacotherapy on learning, was designed to explore a paradigm for measuring effects of mechanism-targeted treatment in fragile X syndrome (FXS). In FXLEARN, the effects of metabotropic glutamate receptor type 5 (mGluR5) negative allosteric modulator (NAM) AFQ056 on language learning were evaluated in 3- to 6-year-old children with FXS, expected to have more learning plasticity than adults, for whom prior trials of mGluR5 NAMs have failed.METHODSAfter a 4-month single-blind placebo lead-in, participants were randomized 1:1 to AFQ056 or placebo, with 2 months of dose optimization to the maximum tolerated dose, then 6 months of treatment during which a language-learning intervention was implemented for both groups. The primary outcome was a centrally scored videotaped communication measure, the Weighted Communication Scale (WCS). Secondary outcomes were objective performance-based and parent-reported cognitive and language measures.RESULTSFXLEARN enrolled 110 participants, randomized 99, and had 91 who completed the placebo-controlled period. Although both groups made language progress and there were no safety issues, the change in WCS score during the placebo-controlled period was not significantly different between the AFQ056 and placebo-treated groups, nor were there any significant between-group differences in change in any secondary measures.CONCLUSIONDespite the large body of evidence supporting use of mGluR5 NAMs in animal models of FXS, this study suggests that this mechanism of action does not translate into benefit for the human FXS population and that better strategies are needed to determine which mechanisms will translate from preclinical models to humans in genetic neurodevelopmental disorders.TRIAL REGISTRATIONClincalTrials.gov NCT02920892.FUNDING SOURCESNeuroNEXT network NIH grants U01NS096767, U24NS107200, U24NS107209, U01NS077323, U24NS107183, U24NS107168, U24NS107128, U24NS107199, U24NS107198, U24NS107166, U10NS077368, U01NS077366, U24NS107205, U01NS077179, and U01NS077352; NIH grant P50HD103526; and Novartis IIT grant AFQ056X2201T for provision of AFQ056.

As the primary Ca2+ release channel in skeletal muscle sarcoplasmic reticulum (SR), mutations in type 1 ryanodine receptor (RyR1) or its binding partners underlie a constellation of muscle disorders, including malignant hyperthermia (MH). In patients with MH mutations, triggering agents including halogenated volatile anaesthetics bias RyR1 to an open state resulting in uncontrolled Ca2+ release, increased sarcomere tension, and heat production. Propofol does not trigger MH and is commonly used for patients at risk of MH. The atomic-level interactions of any anaesthetic with RyR1 are unknown. RyR1 opening was measured by [3H]ryanodine binding in heavy SR vesicles (wild type) and single-channel recordings of MH mutant R615C RyR1 in planar lipid bilayers, each exposed to propofol or the photoaffinity ligand analogue m -azipropofol (AziP m). Activator-mediated wild-type RyR1 opening as a function of propofol concentration was measured by Fura-2 Ca2+ imaging of human skeletal myotubes. AziP m binding sites, reflecting propofol binding, were identified on RyR1 using photoaffinity labelling. Propofol binding affinity to a photoadducted site was predicted using molecular dynamics (MD) simulation. Both propofol and AziP m decreased RyR1 opening in planar lipid bilayers (P <0.01) and heavy SR vesicles, and inhibited activator-induced Ca2+ release from human skeletal myotube SR. Several putative propofol binding sites on RyR1 were photoadducted by AziP m. MD simulation predicted propofol K D values of 55.8 μM and 1.4 μM in the V4828 pocket in open and closed RyR1, respectively. Propofol demonstrated direct binding and inhibition of RyR1 at clinically plausible concentrations, consistent with the hypothesis that propofol partially mitigates malignant hyperthermia by inhibition of induced Ca2+ flux through RyR1. [ABSTRACT FROM AUTHOR]

Simple Summary: Intrapleural hyperthermic chemotherapy is a viable treatment option for malignant pleural effusion in advanced lung cancer. This study explored the effects of hyperthermic chemotherapy with cisplatin on lung cancer cells, including drug-resistant patient-derived tumor cells. By raising the temperature to 43 °C during treatment, we observed significantly enhanced antitumor efficacy and cancer cell death in both 2D and 3D cultures, as well as in a patient-derived xenograft model. The study showed that hyperthermia not only increased the efficacy of cisplatin but also promoted tumor necrosis and altered the expression of proteins associated with cancer cell survival. These findings suggest that hyperthermic chemotherapy may be a promising approach for improving treatment outcomes in patients with drug-resistant lung cancer. Background/Objectives: Malignant pleural effusion (MPE) in lung cancer indicates systemically disseminated advanced lung cancer and is associated with poor survival. Intrapleural hyperthermic chemotherapy (IPHC) is a promising treatment for MPE; however, its biological basis is not fully understood. IPHC can enhance anticancer drug efficacy, particularly in drug-resistant cancers. This study investigated the effects of hyperthermia on cisplatin cytotoxicity in lung cancer cell lines, patient-derived tumor cells, and a patient-derived xenograft (PDX) model. Methods: Lung cancer cell lines (A549 and H2170) and patient-derived tumor cells were cultured in 2D/3D systems and treated with cisplatin under varying temperatures (37 °C, 43 °C, and 45 °C) and exposure times (5, 15, and 30 min). Antiproliferative effects were evaluated using LDH and CCK-8 assays. Optimal conditions identified in cell culture experiments were validated using a PDX model; tumor growth inhibition, delay, and protein expression were analyzed post-treatment. Results: Hyperthermia significantly enhanced the antitumor efficacy of cisplatin at 43 °C and 45 °C, with comparable effects under 15 and 30 min exposure. In the PDX model, IPHC showed increased tumor inhibition and necrosis and delayed tumor regrowth, particularly at higher cisplatin doses. Protein expression analysis revealed that hyperthermia decreased EGFR expression and increased levels of apoptosis-related proteins, including cleaved PARP and caspase-3. Conclusions: IPHC with cisplatin demonstrated enhanced antitumor efficacy in vitro models, particularly in drug-resistant lung cancer, indicating its potential as a valuable adjunct to existing treatment regimens for lung cancer and for improving patient outcomes in advanced lung cancer with MPE or pleural metastasis. [ABSTRACT FROM AUTHOR]

Pathogenic variants in the ryanodine receptor 1 (RYR1) gene are causative for a wide spectrum of muscular phenotypes, ranging from malignant hyperthermia over mild, non-progressive to severe congenital myopathy. Both autosomal dominant and recessive inheritance can occur, with the more severe forms usually showing recessive inheritance. However, genotype–phenotype correlations are complicated due to the large size of the gene and heterogeneous phenotypes. We present a 6-year-old patient with severe congenital myopathy, carrying a heterozygous pathogenic RYR1 variant inherited from the healthy mother. Through whole genome sequencing we identified a second, deep intronic RYR1 variant that has recently been described in another patient with severe congenital myopathy and shown to affect splicing. Segregation analyses confirmed the variants to be compound heterozygous. We compared our patient's phenotype to that of the patient from the literature as well as five additional patients with compound heterozygous RYR1 variants from our center. The main overlapping features comprised congenital onset, predominant muscular hypotonia, and normal creatine kinase (CK) levels, while overall clinical expression varied substantially. Interestingly, both patients carrying the new intronic splice variant showed a very severe disease course. More widespread use of genome sequencing will open the way for better genotype–phenotype correlations. [ABSTRACT FROM AUTHOR]

Malignant hyperthermia susceptibility (MHS) designates individuals at risk of developing a hypermetabolic reaction triggered by halogenated anaesthetics or the depolarising neuromuscular blocking agent suxamethonium. Over the past few decades, beyond the operating theatre, myopathic manifestations impacting daily life are increasingly recognised as a prevalent phenomenon in MHS patients. At the request of the European Malignant Hyperthermia Group, we reviewed the literature and gathered the opinion of experts to define MHS-related myopathy as a distinct phenotype expressed across the adult lifespan of MHS patients unrelated to anaesthetic exposure; this serves to raise awareness about non-anaesthetic manifestations, potential therapies, and management of MHS-related myopathy. We focused on the clinical presentation, biochemical and histopathological findings, and the impact on patient well-being. The spectrum of symptoms of MHS-related myopathy encompasses muscle cramps, stiffness, myalgias, rhabdomyolysis, and weakness, with a wide age range of onset mainly during adulthood. Histopathological analysis can reveal nonspecific abnormalities suggestive of RYR1 involvement, while metabolic profiling reflects altered energy metabolism in MHS muscle. Myopathic manifestations can significantly impact patient quality of life and lead to functional limitations and socio-economic burden. While currently available therapies can provide symptomatic relief, there is a need for further research into targeted treatments addressing the underlying pathophysiology. Counselling early after establishing the MHS diagnosis, followed by multidisciplinary management involving various medical specialties, is crucial to optimise patient care. [ABSTRACT FROM AUTHOR]

To avoid inhalational anesthetics, total intravenous anesthesia (TIVA) is required in patients with a predisposition to malignant hyperthermia (MH). However, propofol, which is frequently used, may be avoided in patients with egg allergies because of the contraindications in the drug information. Furthermore, some patients may not consent to the use of propofol. We report a case of TIVA using midazolam and dexmedetomidine as substitutes for propofol in a pediatric patient with egg allergy and a predisposition to MH. A 10-year-old boy was scheduled to undergo perforated drainage of an epidural abscess. He had egg allergy, and his uncle had been diagnosed with MH. He also developed a generalized drug eruption caused by antibiotics. Concerned about allergic reactions, he and his parents did not consent to administrating propofol. The patient’s perioperative course was uneventful. The combination of midazolam and dexmedetomidine may be a useful option as substitutes for propofol.

Abstract Background Limited research has been conducted on how healthcare simulation can mitigate clinician stress. Stress exposure training (SET) has been shown to decrease stress’s impact on performance. Combining SET with virtual reality (VR) simulation training has not yet been explored in the context of stress inoculation. The primary purpose of this pilot study was to determine if a VR module could induce stress. The secondary purpose was to determine if repeated exposure to stressors could decrease stress response in a simulated environment. Methods Medical students were recruited to partake in VR simulation modules aimed at treatment of malignant hyperthermia (MH). Those in the SET group were exposed to stressful stimuli during training modules, while those in the Control group were not. Both groups then completed a Test Module with the presence of stressful stimuli. Objective and subjective indicators of stress were measured after each module. Results Both groups indicated increases in perceived stress and module stressfulness after Training Module 1 and decreases after Training Module 2. After the Test Module, the Control group experienced significant elevation in perceived stress (p = .05), and the SET group had a significant decrease in perceived module stressfulness (p

Neuroleptic Malignant Syndrome (NMS) is a rare and potentially fatal complication that can occur after exposure to dopamine-blocking drugs, especially antipsychotic medications. Symptoms of NMS include fever, severe muscle rigidity, and dysautonomia. The exact cause of NMS is not known, but it is believed to be related to the blockade of dopamine receptors in the central nervous system. NMS can be difficult to diagnose, as it can mimic other disorders such as serotonin syndrome, malignant hyperthermia, and anti-NMDA receptor encephalitis. Treatment for NMS is empirical and typically involves muscle relaxants and close monitoring in an intensive care unit. While the risk of recurrence is low, some risk remains. [Extracted from the article]

ABSTRACT Emergency Department (ED) presentations for Mental Health (MH) help‐seeking have been rising rapidly, with EDs as the main entry point for most individuals in Australia. The objective of this retrospective cohort study was to analyse the sociodemographic and presentation features of people who sought mental healthcare in two EDs located in a regional coastal setting in New South Wales (NSW), Australia from 2016 to 2021. This article is a part of a broader research study on the utilisation of machine learning in MH. The objective of this study is to identify the factors that lead to the admission of individuals to an MH inpatient facility when they seek MH care in an ED. Data were collected using existing records and analysed using descriptive univariate analysis with statistical significance between the two sites was determined using Chi squared test, p < 0.05. Two main themes characterise dominant help‐seeking dynamics for MH conditions in ED, suicidal ideation, and access and egress pathways. The main findings indicate that suicidal ideation was the most common presenting problem (38.19%). People presenting to ED who ‘Did not wait’ or ‘Left at own risk’ accounted for 10.20% of departures from ED. A large number of presentations arrived via the ambulance, accounting for 45.91%. A large proportion of presentations are related to a potentially life‐threatening condition (suicidal ideation). The largest proportion of triage code 1 ‘Resuscitation’ was for people with presenting problem of ‘Behavioural Disturbance’. Departure and arrival dynamics need to be better understood in consultation with community and lived experience groups to improve future service alignment with the access and egress pathways for emergency MH care. [ABSTRACT FROM AUTHOR]

Awake surgery has been applied for various surgical procedures with positive outcomes; however, in neurosurgery, the technique has traditionally been reserved for cranial surgery. Awake surgery for the spine (ASFS) is an alternative to general anesthesia (GA). As early studies report promising results, ASFS is progressively gaining more interest from spine surgeons. The history defining the range of adverse events facing patients undergoing GA has been well described. Adverse reactions resulting from GA can include postoperative nausea and vomiting, hemodynamic instability and cardiac complications, acute kidney injury or renal insufficiency, atelectasis, pulmonary emboli, postoperative cognitive dysfunction, or malignant hyperthermia and other direct drug reactions. For this reason, many high-risk populations who have typically been poor candidates under classifications for GA could benefit from the many advantages of ASFS. This narrative review will discuss the significant historical components related to ASFS, pertinent mechanisms of action, protocol overview, and the current trajectory of spine surgery with ASFS. [ABSTRACT FROM AUTHOR]

Skeletal muscle, the major processor of dietary glucose, stores it in myriad glycogen granules. Their numbers vary with cellular location and physiological and pathophysiological states. AI models were developed to derive granular glycogen content from electron-microscopic images of human muscle. Two UNet-type semantic segmentation models were built: "Locations" classified pixels as belonging to different regions in the cell; "Granules" identified pixels within granules. From their joint output, a pixel fraction pf was calculated for images from patients positive (MHS) or negative (MHN) to a test for malignant hyperthermia susceptibility. pf was used to derive vf, the volume fraction occupied by granules. The relationship vf (pf) was derived from a simulation of volumes ("baskets") containing virtual granules at realistic concentrations. The simulated granules had diameters matching the real ones, which were measured by adapting a utility devised for calcium sparks. Applying this relationship to the pf measured in images, vf was calculated for every region and patient, and from them a glycogen concentration. The intermyofibrillar spaces and the sarcomeric I band had the highest granular content. The measured glycogen concentration was low enough to allow for a substantial presence of non-granular glycogen. The MHS samples had an approximately threefold lower concentration (significant in a hierarchical test), consistent with earlier evidence of diminished glucose processing in MHS. The AI models and the approach to infer three-dimensional magnitudes from twodimensional images should be adaptable to other tasks on a variety of images from patients and animal models and different disease conditions. [ABSTRACT FROM AUTHOR]

Introduction and purpose: The number of invented and produced medications has increased over recent years. Besides their positive impact on health, they invariably provide various kinds of side effects. This review is focused on malignant neuroleptic syndrome, a rare condition with no fully confirmed pathogenesis, which at least partially can be explained as an adverse effect of blocking dopamine receptors. Even though it usually affects psychiatric or neurological patients, doctors of all medical specializations should stay alert, as the condition can often lead to premature death. Brief description of knowledge: The main symptoms associated with NMS are hypertonia, hyperpyrexia, autonomic instability and altered consciousness. They can appear in any configuration, sometimes followed by less characteristic manifestations. It should be primarily differentiated from serotonin syndrome, malignant hyperpyrexia and catatonia, mostly through the interview of those who have taken medications and undergone surgeries, as there are not any specific lab tests available. Fundamental treatment methods consist of neuroleptic withdrawal, intensive supportive care, drug administration and eventually ECT. Summary: NMS is an uncommon, severe disease that should be carefully considered in patients treated with neuroleptics. Due to its rarity and sudden onset, it appears to be problematic to conduct widespread research and studies, so there are still no concrete, consistent and unquestioned guidelines on recognizing and treating the condition. [ABSTRACT FROM AUTHOR]

Background: Aberrant activation of macrophages is associated with pathogenesis of acute lung injury (ALI). However, the potential pathogenesis has not been explored. Objectives: We aimed to identify whether histone deacetylase (HDAC) 10 is involved in lipopolysaccharide (LPS)-exposed ALI and reveal the underlying pathogenesis by which it promotes lung inflammation in LPS-exposed ALI via modifying P62 with deacetylation. Methods: We constructed an ALI mice model stimulated with LPS to determine the positive effect of Hdac10 deficiency. Moreover, we cultured murine alveolar macrophage cell line (MH-S cells) and primary bone marrow-derived macrophages (BMDMs) to explore the pro-inflammatory activity and mechanism of HDAC10 after LPS challenge. Results: HDAC10 expression was increased both in mice lung tissues and macrophage cell lines and promoted inflammatory cytokines production exposed to LPS. Hdac10 deficiency inhibited autophagy and inflammatory response after LPS stimulation. In vivo, Hdac10fl/fl-LysMCre mice considerably attenuated lung inflammation and inflammatory cytokines release exposed to LPS. Mechanistically, HDAC10 interacts with P62 and mediates P62 deacetylation at lysine 165 (K165), by which it promotes P62 expression and increases inflammatory cytokines production. Importantly, we identified that Salvianolic acid B (SAB), an HDAC10 inhibitor, reduces lung inflammatory response in LPS-stimulated ALI. Conclusion: These results uncover a previously unknown role for HDAC10 in regulating P62 deacetylation and aggravating lung inflammation in LPS-induced ALI, implicating that targeting HDAC10 is an effective therapy for LPS-exposed ALI. [ABSTRACT FROM AUTHOR]

Flatfoot (pes planus) is a common foot deformity, and its causes are mainly related to age, gender, weight, and genetics. Previous studies have shown that custom-made insoles could have a positive effect in improving plantar pressure and symptoms in individuals with flexible flatfeet, but it remains to be explored whether they can still show benefits in daily walking on different slopes. This study aims to investigate a custom-made insole based on plantar pressure redistribution and to verify its effectiveness by gait analysis on different slopes. We recruited 10 subjects and compared the peak pressure and impulse in each area between custom-made insole (CI) and ordinary insole (OI) groups. The results illustrate that CI raises the pressure in T area, improves the ability of the subjects to move forward in the slope walking, which was beneficial to gait stability. The redistribution of pressure in MF and MH area is promoted to provide active protection for subjects. Meanwhile, CI could decrease the impulse in MF area during uphill and level walking, which effectively reduces the accumulation of fatigue during gait. Moreover, avoiding downhill walking could be able to protect foot from injury in daily life. [ABSTRACT FROM AUTHOR]

Introduction: Beginning in 2019, the Department of Veterans Affairs (VA) prioritized improving access to care nationally to deliver virtual care and implemented 18 regionally based Clinical Resource Hubs (CRHs) to meet this priority. This observational study describes the quantity and types of care delivered by CRH Mental Health teams, and the professions of those hired to deliver it. Methods: A retrospective cohort study, based on national VA CRH mental health care utilization data and CRH staffing data for CRH's first 3 years, was conducted. Results: CRH Mental Health teams primarily used Telemental Health (TMH) to provide care (98.1% of all CRH MH encounters). The most common disorders treated included depression, post-traumatic stress disorder, and anxiety disorders. The amount of care delivered overtime steadily increased as did the racial and ethnic diversity of Veterans served. Psychologists accounted for the largest share of CRH staffing, followed by psychiatrists. Conclusions: CRH TMH delivered from a regional hub appears to be a feasible and acceptable visit modality, based on the continuously increasing CRH TMH visit rates. Our results showed that CRH TMH was predominantly used to address common mental health diagnoses, rather than serious mental illnesses. Traditionally marginalized patient populations increased over the 3-year window, suggesting that CRH TMH resources were accessible to many of these patients. Future research should assess barriers and facilitators for accessing CRH TMH, especially for difficult-to-service patient populations, and should consider whether similar results to ours occur when regional TMH is delivered to non-VA patient populations. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Malignant hyperthermia susceptibility (MHS) is an autosomal dominant pharmacogenetic disorder that manifests as a hypermetabolic state when carriers are exposed to halogenated volatile anesthetics or depolarizing muscle relaxants. In animals, heat stress intolerance is also observed. MHS is linked to over 40 variants in RYR1 that are classified as pathogenic for diagnostic purposes. More recently, a few rare variants linked to the MHS phenotype have been reported in CACNA1S, which encodes the voltage-activated Ca2+ channel CaV1.1 that conformationally couples to RyR1 in skeletal muscle. Here, we describe a knock-in mouse line that expresses one of these putative variants, CaV1.1-R174W. Heterozygous (HET) and homozygous (HOM) CaV1.1-R174W mice survive to adulthood without overt phenotype but fail to trigger with fulminant malignant hyperthermia when exposed to halothane or moderate heat stress. All three genotypes (WT, HET, and HOM) express similar levels of CaV1.1 by quantitative PCR, Western blot, [3H]PN200-110 receptor binding and immobilization-resistant charge movement densities in flexor digitorum brevis fibers. Although HOM fibers have negligible CaV1.1 current amplitudes, HET fibers have similar amplitudes to WT, suggesting a preferential accumulation of the CaV1.1-WT protein at triad junctions in HET animals. Never-the-less both HET and HOM have slightly elevated resting free Ca2+ and Na+ measured with double barreled microelectrode in vastus lateralis that is disproportional to upregulation of transient receptor potential canonical (TRPC) 3 and TRPC6 in skeletal muscle. CaV1.1-R174W and upregulation of TRPC3/6 alone are insufficient to trigger fulminant malignant hyperthermia response to halothane and/or heat stress in HET and HOM mice.

Malignant syndromes represent a group of medical conditions characterized by a rapid evolution of clinical manifestations, potentially leading to life-threatening complications if left untreated. These syndromes pose significant challenges for diagnosis and management, as they can lead to multisystem organ failure and death. Despite distinct features and origins, these syndromes share similar clinical presentation, pathophysiology, and the imperative for urgent medical intervention. While distinct mechanisms may initially trigger the different malignant syndromes, a final common pathway leading to similar signs and symptoms involves various neurotransmitter systems, including dopaminergic, serotonergic, GABAergic, glycinergic, and glutamatergic pathways. This narrative review examines the clinical presentations and potential causes of malignant syndromes, both highlighting shared pathophysiological mechanisms and emphasizing the critical importance of early recognition and intervention to mitigate potentially fatal outcomes. Although clinically heterogeneous, with variable motor and non-motor manifestations, most malignant syndromes share acute and rapid disruptions in physiological functions, including body temperature regulation, metabolism, control of the autonomic system and maintenance of consciousness. The potential for severe morbidity and mortality associated with these syndromes emphasizes the critical need for understanding their clinical characteristics, underlying mechanisms, and appropriate management strategies.

The article discusses the need for mandatory training in the management of rare anaesthetic events, specifically focusing on patient deaths caused by unrecognised oesophageal intubation. The authors highlight that despite efforts to prevent such harm, patients continue to die from this preventable error. They argue that regular, multidisciplinary team training should be implemented to improve performance during these rare events. The authors acknowledge that there is currently no proof that this training will improve outcomes, but they believe it is necessary to prioritize patient safety. They suggest that the General Medical Council should enforce mandatory training for anaesthetists, and they reference the example of Australia and New Zealand where similar training is already in place. The authors acknowledge that implementing career-long mandatory training will come with costs, but they emphasize the importance of protecting patients and preventing future tragedies. [Extracted from the article]

Malignant hyperthermia (MH), a life-threatening complication during general anesthesia, primarily triggers hypermetabolism and skeletal muscle damage. The common MH signs include elevated body temperature, tachycardia, hypercapnia, muscle rigidity, rhabdomyolysis, hyperkalemia, and metabolic acidosis. However, MH-related skin lesions are rarely documented. Here, we present a case of a 3-year-old patient experiencing self-resolving skin rash during an MH episode. A healthy 3-year-old girl underwent strabismus surgery under general anesthesia, displaying the MH episode during the procedure. The significant vital signs included hypercapnia, tachycardia, and hyperthermia, peaking 120 min postinduction. Prompt measures, including sevoflurane discontinuation, hydration, cooling, and alternative anesthesia, swiftly stabilized the patient. Intriguingly, an hour later, an isolated skin rash emerged on the right calf and toes, which gradually resolved without intervention. Postoperative examinations revealed no adverse effects. Despite its rarity, the occurrence of MH-associated skin rashes emphasizes the need for vigilance, especially in pediatric strabismus surgeries, despite minimal documented incidents. In summary, our case highlights the self-limiting nature of MH-related skin rash, occurring post-MH resolution. Its causative mechanisms warrant further investigation. Proactive avoidance of MH trigger agents remains crucial for optimal care during pediatric strabismus surgeries.

Abstract 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.

Abstract Background Malignant hyperthermia (MH) is a rare, life-threatening disorder of calcium homeostasis in skeletal muscle cells that is triggered by volatile anesthetics and succinylcholine, leading to a hypermetabolic reaction. The pathogenic ryanodine receptor 1 (RYR1) gene variant is critical. Patients susceptible to MH should avoid triggering agents, and total intravenous anesthesia (TIVA) is preferred. Remimazolam is safe in patients with suspected MH. Case presentation We present the first case of remimazolam treatment in a genetically confirmed patient with MH without MH development. A 72-year-old man with a family history of MH underwent remimazolam-based TIVA. After informed consent was obtained, a muscle biopsy and genetic testing were performed. Intraoperatively and postoperatively, the patient exhibited no signs of MH. An enhanced function of the RYR1 channel into releasing calcium was indicated, and the genetic testing revealed a pathogenic variant of RYR1. Conclusions Remimazolam-based TIVA is safe in patients confirming the diagnosis of MH.

Background: Non-suicidal self-injury (NSSI) has exhibited an increasing trend in recent years and is now globally recognized as a major public health problem among adolescents and young adults. Negative life events (NLEs) are positively associated with NSSI. We sought to explore (1) whether sex plays a role in the risk of NLEs leading to NSSI and (2) the role played by mental health (MH). Methods: We adopted a multi-stage cluster sampling method to select college students across four grades from May to June 2022. Generalized linear models were used to evaluate the relationships between NLEs, sex, MH and NSSI, presented as incidence-rate ratios (RRs) with 95% confidence intervals (CIs). We examined the complex relationship between these variables using the PROCESS method for moderation analysis. Results: Following the exclusion of data that did not meet the study requirements, data from 3,578 students (mean age: 20.53 [± 1.65] years) were included. Poisson regression results indicate that high-level NLEs (RR = 0.110, 95%CI: 0.047–0.173) are associated with increased NSSI. Furthermore, interaction effects were observed among sex, NLEs and NSSI. MH and sex moderated the relationship between NLEs and NSSI. Conclusion: Identifying risk factors for NSSI is also important when exploring the interaction between NLEs and MH given the potential for NSSI to significantly increase the risk of later psychopathological symptoms and substance abuse problems. In addition, the significance of sex differences in risk factors for NSSI should be determined. This study evaluated how the impact of NLEs on NSSI can be reduced among adolescents from multiple perspectives. [ABSTRACT FROM AUTHOR]

Background: The intraoperative use of tourniquets is associated with several complications, including hyperthermia. We present the first documented case of tourniquet-induced hyperthermia in a pediatric patient at our institution. Case: A 5-year-old female with no past medical history underwent tendon release surgery for congenital talipes equinovarus under general anesthesia. Following inflation of a pneumatic tourniquet to a pressure of 250 mmHg on her left thigh, the patient experienced a gradual increase in body temperature. Despite the implementation of cooling measures, the temperature continued to increase until it plateaued. The hyperthermia gradually resolved upon deflation of the tourniquet. Conclusions: Tourniquet-induced hyperthermia should be considered as a potential cause of intraoperative hyperthermia, particularly in the absence of typical signs of malignant hyperthermia. Early recognition and appropriate management, including deflation of the tourniquet and implementation of cooling measures, are crucial for preventing potential complications associated with hyperthermia. [ABSTRACT FROM AUTHOR]

Aim The study aims to review all the genetically confirmed STAC3-related myopathy being followed in a single center in the Eastern Province of Saudi Arabia. Methodology A retrospective review of all genetically confirmed STAC3-related myopathy followed in our clinic has been conducted. Results 7 patients with STAC3-related myopathy have been found in our cohort, with all the patients presenting with infantile hypotonia, myopathic facies, and muscle weakness in the first year of life. Feeding difficulties and failure to thrive were found in all patients except one who died during the neonatal period. Respiratory muscle involvement was also found in 5 out of 6 formally tested patients while cleft palate was found in 5 patients. Conclusion STAC3-related myopathy is a relatively rare, malignant hyperthermia (MH)--causing muscle disease described in specific, highly consanguineous populations. Making the diagnosis in myopathic patients with cleft palate preoperatively can prevent MH-induced, anesthesia-related perioperative complications. [ABSTRACT FROM AUTHOR]

Congenital myopathy type 13 (CMYO13), also known as Native American myopathy, is a rare muscle disease characterized by early-onset hypotonia, muscle weakness, delayed motor milestones, and susceptibility to malignant hyperthermia. The phenotypic spectrum of congenital myopathy type 13 is expanding, with milder forms reported in non-native American patients. The first description of the disease dates to 1987 when Bailey and Bloch described an infant belonging to a Native American tribe with cleft palate, micrognathia, arthrogryposis, and general-anesthesia-induced malignant hyperthermia reaction; the cause of the latter remains poorly defined in this rare disease. The pan-ethnic distribution, as well as its predisposition to malignant hyperthermia, makes the identification of CMYO13 essential to avoid life-threatening, anesthesia-related complications. In this article, we are going to review the clinical phenotype of this disease and the pathophysiology of this rare disease with a focus on two unique features of the disease, namely cleft palate and malignant hyperthermia. We also highlight the importance of recognizing this disease's expanding phenotypic spectrum—including its susceptibility to malignant hyperthermia—and providing appropriate care to affected individuals and families. [ABSTRACT FROM AUTHOR]

Summary: The 7th National Audit Project of the Royal College of Anaesthetists studied peri‐operative cardiac arrest. An activity survey estimated UK paediatric anaesthesia annual caseload as 390,000 cases, 14% of the UK total. Paediatric peri‐operative cardiac arrests accounted for 104 (12%) reports giving an incidence of 3 in 10,000 anaesthetics (95%CI 2.2–3.3 per 10,000). The incidence of peri‐operative cardiac arrest was highest in neonates (27, 26%), infants (36, 35%) and children with congenital heart disease (44, 42%) and most reports were from tertiary centres (88, 85%). Frequent precipitants of cardiac arrest in non‐cardiac surgery included: severe hypoxaemia (20, 22%); bradycardia (10, 11%); and major haemorrhage (9, 8%). Cardiac tamponade and isolated severe hypotension featured prominently as causes of cardiac arrest in children undergoing cardiac surgery or cardiological procedures. Themes identified at review included: inappropriate choices and doses of anaesthetic drugs for intravenous induction; bradycardias associated with high concentrations of volatile anaesthetic agent or airway manipulation; use of atropine in the place of adrenaline; and inadequate monitoring. Overall quality of care was judged by the panel to be good in 64 (62%) cases, which compares favourably with adults (371, 52%). The study provides insight into paediatric anaesthetic practice, complications and peri‐operative cardiac arrest. [ABSTRACT FROM AUTHOR]

Introduction: Implementation science (IS) offers methods to systematically achieve the Ending the HIV Epidemic goals in the United States, as well as the global UNAIDS targets. Federal funders such as the National Institutes of Mental Health (NIMH) have invested in implementation research to achieve these goals, including supporting the AIDS Research Centres (ARCs), which focus on high‐impact science in HIV and mental health (MH). To facilitate capacity building for the HIV/MH research workforce in IS, "grey areas," or areas of IS that are confusing, particularly for new investigators, should be addressed in the context of HIV/MH research. Discussion: A group of IS experts affiliated with NIMH‐funded ARCs convened to identify common and challenging grey areas. The group generated a preliminary list of 19 grey areas in HIV/MH‐related IS. From the list, the authors developed a survey which was distributed to all ARCs to prioritize grey areas to address in this paper. ARC members across the United States (N = 60) identified priority grey areas requiring clarification. This commentary discusses topics with 40% or more endorsement. The top grey areas that ARC members identified were: (1) Differentiating implementation strategies from interventions; (2) Determining when an intervention has sufficient evidence for adaptation; (3) Integrating recipient perspectives into HIV/MH implementation research; (4) Evaluating whether an implementation strategy is evidence‐based; (5) Identifying rigorous approaches for evaluating the impact of implementation strategies in the absence of a control group or randomization; and (6) Addressing innovation in HIV/MH IS grants. The commentary addresses each grey area by drawing from the existing literature (when available), providing expert guidance on addressing each in the context of HIV/MH research, and providing domestic and global HIV and HIV/MH case examples that address these grey areas. Conclusions: HIV/MH IS is key to achieving domestic and international goals for ending HIV transmission and mitigating its impact. Guidance offered in this paper can help to overcome challenges to rigorous and high‐impact HIV/MH implementation research. [ABSTRACT FROM AUTHOR]

Introduction We report a series of patients in three different Libyan families diagnosed with congenital myopathy to study the wide clinical variability between these families, and the genetic heterogeneity. Description of Cases We describe six patients, one patient presented with severe neonatal-onset RYR1-associated myopathy while the other five patients came mainly due to delay in motor development; genetic testing confirmed the diagnosis of CMY-1B disease due to RYR1 mutation in all patients. Clinical features of congenital widely varied between the families ranging from profound hypotonia during the neonatal period in one family to a motor delay and abnormal gait during childhood in other two families. Whereas the clinical picture is quite similar in the patients of same family, the patient who presented with severe neonatal presentation of RYR1-associated myopathy also had gastrostomy feeding, respiratory involvement, clubfeet, cleft palate, and undescended testes. The five patients who presented due to delay in motor development all were ambulatory without the need of support, except the youngest one aged 4 years still walking with support. The genetic study in the form of whole-exon sequencing as well as next-generation sequencing showed homozygosity of a gene mutation in five patients and a compound heterozygosity in one patient which presented with neonatal severe hypotonia. Conclusion CMY-1B disease is a rare autosomal dominant and recessive genetic disorder that has variable clinical presentations. The early diagnosis is very important for genetic counseling as well as avoiding malignant hyperthermia. We also report rare and unusual presentations that may further delay the diagnosis. [ABSTRACT FROM AUTHOR]

Background: The causes of perioperative hyperlactatemia vary, but they are generally associated with hypoperfusion. Here, we report the case of a pediatric patient who developed unexplained hyperlactatemia during anesthesia with propofol and sevoflurane, which recurred during a second surgery under anesthesia with remimazolam. Case presentation. An 8-year-old boy with Perthes disease and no remarkable past or family history was scheduled for an osteotomy. Anesthesia was induced with propofol and rocuronium and then maintained with sevoflurane and remifentanil. The patient developed lactic acidosis without hemodynamic instability during anesthesia, with a normal lactate/pyruvate ratio after surgery, suggesting a lack of hypoperfusion. We used remimazolam instead of propofol during the second surgery 6 months later, considering the possibility of drug-induced lactic acidosis, including malignant hyperthermia and propofol infusion syndrome, where the unexplained hyperlactatemia recurred. Conclusions: Distinguishing the causes of hyperlactatemia, particularly in the absence of other symptoms, is challenging. The lactate/pyruvate ratio during episodes of hyperlactatemia can provide insights into the underlying pathology. [ABSTRACT FROM AUTHOR]

Patients with neuromuscular diseases are particularly vulnerable in the perioperative period to the development of pulmonary and cardiac complications, or medication side effects. These risks could include hypoventilation, aspiration pneumonia, exacerbation of underlying cardiomyopathy, arrhythmias, adrenal insufficiency, prolonged neuromuscular blockade, issues related to thermoregulation, rhabdomyolysis, malignant hyperthermia, or prolonged mechanical ventilation. Interventions at each of the perioperative stages can be implemented to mitigate these risks. A careful pre-operative evaluation may help identify risk factors so that appropriate interventions are initiated, including cardiology consultation, pulmonary function tests, initiation of noninvasive ventilation, or implementation of preventive measures. Important intraoperative issues include positioning, airway and anesthetic management, and adequate ventilation. The postoperative period may require correction of electrolyte abnormalities, control of secretions with medications, manual or mechanical cough assistance, avoiding the risk of reintubation, judicious pain control, and appropriate medication management. The aim of this review is to increase awareness of the particular surgical challenges in this vulnerable population, and guide the clinician on the various evaluations and interventions that may result in a favorable surgical outcome. [ABSTRACT FROM AUTHOR]

Purpose: In the current study, the clinical efficacy of iodine-125 (125I) radioactive particle implantation with deep hyperthermia in malignant tumor treatment was retrospectively analyzed. Material and methods: Sixty patients with malignant tumors treated at Zhongshan Hospital affiliated with Dalian University, from January 2021 to January 2023, were included in this retrospective analysis. Computed tomography (CT)-guided 125I radioactive particles were implanted into lesions, followed by deep hyperthermia administered for 3 days after surgery. Lesion size was evaluated monthly using CT or magnetic resonance imaging (MRI), and objective response rate (ORR) and local control rate (DCR) were calculated. Mean pain numerical score and European Organization for Research and Treatment of Cancer quality of life core scale C30 (EORTC QLQ-C30 v. 3.0) were assessed pre-treatment and post-treatment, and post-operative adverse reactions were comparatively analyzed. Results: After 6 months, the combined treatment resulted in a 73.33% ORR and an 81.67% DCR among 60 patients experiencing pre-treatment pain, and 49 (81.67%) exhibited effective pain relief. EORTC QLQ-C30 v. 3.0 evaluation revealed improved quality of life post-treatment. Adverse reactions during combined treatment were mitigated with targeted supportive measures, and no adverse reactions of level 2 or higher were observed. Conclusions: 125I radioactive particle implantation with deep hyperthermia is shown to be an effective combination therapy for malignant tumors, yielding significant clinical efficacy. Notably, it enhances patient quality of life, reduces tumor burden, mitigates adverse reactions, and alleviates pain. Given its minimal trauma and mild adverse reactions, this combination therapy warrants widespread clinical application. [ABSTRACT FROM AUTHOR]

Purpose Mucosal inflammation is a key feature of ulcerative colitis (UC), a chronic relapsing and remitting form of inflammatory bowel disease. Omentin-1, a newly discovered adipokine, is reported to have anti-inflammatory effects and has been found to be decreased in patients with inflammatory bowel disease. The aim of our study was to investigate the association between serum omentin-1 levels and mucosal disease activity in patients with UC. Study design A total of 126 patients with UC and 77 healthy volunteers were enrolled in the study. Serum omentin-1 expression levels were measured using enzyme-linked immunosorbent assay to evaluate its potential for monitoring disease activity, including clinical and endoscopic activity. Results Serum omentin-1 levels were significantly lower in patients with UC compared to healthy controls (HC) (UC, 61.7 interquartile range: 51.5–72.6 versus healthy controls, 103.5 interquartile range: 48.3–156.2 ng/ml; P  < .001). Furthermore, serum omentin-1 levels were associated with both clinical and endoscopic activity in patients with UC. Notably, omentin-1 levels were significantly lower in patients who achieved mucosal healing. Receiver operating characteristic curves indicated that serum omentin-1 levels could potentially serve as an activity index for evaluating UC. Conclusions These findings provide further insight into the association between omentin-1 and UC, suggesting that omentin-1 may be a useful biomarker for monitoring mucosal disease activity in patients with UC. Key message What is already known on this topic?   UC is a chronic inflammatory bowel disease characterized by mucosal inflammation. MH is an important treatment goal, as failure to achieve MH predicts clinical relapse. Serum omentin-1, an adipokine with anti-inflammatory properties, has shown reduced levels in patients with IBD. What this study adds?   Our study revealed significantly lower serum omentin-1 levels in UC patients compared to healthy controls. Serum omentin-1 levels were associated with clinical and endoscopic activity and might indicate MH. How this study might affect research, practice, or policy?   Our findings suggest that measuring serum omentin-1 levels could serve as a potential biomarker for monitoring mucosal disease activity in UC. Incorporating omentin-1 assessment into clinical practice may aid in early detection of disease activity and monitoring treatment response. [ABSTRACT FROM AUTHOR]

Background: Statins are commonly used medications. Variants in SLCO1B1, CYP2C9, and ABCG2 are known predictors of muscle effects when taking statins. More exploratory genes include RYR1 and CACNA1S, which can also be associated with disease conditions. Methods: Patients with pathogenic/likely pathogenic variants in RYR1 or CACNA1S were identified through an elective genomic testing program. Through chart review, patients with a history of statin use were assessed for statin-associated muscle symptoms (SAMS) along with collection of demographics and other known risk factors for SAMS. Results: Of the 23 patients who had a pathogenic or likely pathogenic RYR1 or CACNA1S variant found, 12 had previous statin use; of these, SAMS were identified in four patients. Conclusion: These data contribute to previous literature suggesting patients with RYR1 variants may have an increased SAMS risk. Additional research will be helpful in further investigating this relationship and providing recommendations. Summary points Statins are commonly used medications to treat high cholesterol and to prevent cardiovascular disease. Discontinuation of statins is often due to statin-associated muscle symptoms (SAMS). Gene variants known to be predictors of SAMS include variants in SLCO1B1, CYP2C9, ABCG2, CPT2, PYGM, AMPD1, PHKA1, LPIN1, CNBP, RYR1, and CACNA1S. Elective genetic testing often includes RYR1 and CACNA1S because of their association with malignant hyperthermia susceptibility, and therefore increasing numbers of patients are incidentally identified to have variants in these genes. This study examined 23 patients from a single health system who had identified pathogenic or likely pathogenic variants for RYR1 or CACNA1S, of whom 12 were current or past statin users. Four patients had evidence of SAMS, of whom three had documented statin intolerance noted in the electronic health record. RYR1 and CACNA1S should be further investigated as a potential risk factor for SAMS. [ABSTRACT FROM AUTHOR]

This article presents a case study of a 9-year-old Arabian gelding that was referred for hyporexia and pigmenturia after a trail ride. The horse exhibited severe azotemia and increased muscle enzyme activities. Cystoscopy revealed red filamentous material in the urine, and urine cytology showed acute renal tubular injury with neutrophilic inflammation. Despite treatment, the horse developed progressive azotemia and oliguria and was euthanized. Postmortem examination revealed acute renal tubular necrosis secondary to myoglobinuric nephropathy. The article discusses the unique gross and microscopic morphology of pigment-containing casts in horses with acute kidney injury. [Extracted from the article]

Background: Malignant hyperthermia (MH) is a rare, life-threatening disorder of calcium homeostasis in skeletal muscle cells that is triggered by volatile anesthetics and succinylcholine, leading to a hypermetabolic reaction. The pathogenic ryanodine receptor 1 (RYR1) gene variant is critical. Patients susceptible to MH should avoid triggering agents, and total intravenous anesthesia (TIVA) is preferred. Remimazolam is safe in patients with suspected MH. Case presentation: We present the first case of remimazolam treatment in a genetically confirmed patient with MH without MH development. A 72-year-old man with a family history of MH underwent remimazolam-based TIVA. After informed consent was obtained, a muscle biopsy and genetic testing were performed. Intraoperatively and postoperatively, the patient exhibited no signs of MH. An enhanced function of the RYR1 channel into releasing calcium was indicated, and the genetic testing revealed a pathogenic variant of RYR1. Conclusions: Remimazolam-based TIVA is safe in patients confirming the diagnosis of MH. [ABSTRACT FROM AUTHOR]

Moral injury syndrome (MIS) is a mental health (MH) problem that substantially affects resilience; the presence of MIS reduces responsiveness to psychotherapy and increases suicide risk. Evidence-based treatment for MIS is available; however, it often goes untreated. This project uses principles of the Consolidated Framework for Implementation Research (CFIR) to assess barriers and facilitators to the implementation of Building Spiritual Strength (BSS), a multi-disciplinary treatment for MIS. Interviews were conducted with chaplains and mental health providers who had completed BSS facilitator training at six sites in the VA. Data were analyzed using the Hamilton Rapid Turnaround method. Findings included multiple facilitators to the implementation of BSS, including its accessibility and appeal to VA chaplains; leadership by VA chaplains trained in the intervention; and effective collaboration between the chaplains and mental health providers. Barriers to the implementation of BSS included challenges in engaging mental health providers and incorporating them as group leaders, veterans' lack of familiarity with the group format of BSS, and the impact of the COVID-19 pandemic. Results highlight the need for increased trust and collaboration between VA chaplains and mental health providers in the implementation of BSS and treatment of MIS. [ABSTRACT FROM AUTHOR]

This article provides an overview of novel psychoactive substances (NPS), which are synthetic derivatives of illicit drugs. NPS are often marketed as safe and legal alternatives, but they lack regulation and can contain varying amounts of substances. They are not easily detected on routine tests and can have uncommon clinical presentations. The article discusses different categories of NPS, such as stimulants and hallucinogens, and provides information on their diagnosis and management. It also highlights the challenges faced by healthcare providers in combating NPS use. The document emphasizes the importance of a thorough history and physical examination for diagnosing and managing acute intoxication or overdose. [Extracted from the article]

Background: Malignant hyperthermia (MH), a rare inherited condition seen almost exclusively in the perioperative setting, is triggered by volatile anesthetics or an intravenous paralytic drug, succinylcholine. It can, however, occur without any exposure to anesthetic drugs, being associated with heat illness and rhabdomyolysis, thus presenting a little-known risk to young athletes exercising in hot environments. Objective: This study aimed to determine the first responder awareness of MH and its association with heat illness in young athletes within athletic and clinical environments. Methods: Awareness within the clinical milieu was assessed by an institutional chart review of 3296 charts. The identified heat illness cases were examined for treatment consistent with the management of a suspected episode of MH. Awareness among first responders in an athletic setting was examined by a survey administered to a total of 1,500 coaches and athletic trainers at the high school level along with emergency medical services providers across the United States. Results: No treatment consistent with the suspicion of MH was noted among clinical first responders, suggesting a lack of awareness. Survey administration also revealed a limited amount of knowledge of MH and its potential role in heat illness. Conclusion: The results point to lack of awareness among pre-hospital and hospital-based first responders of the relationship between MH and heat illness in young athletes. An effort to educate these members of the healthcare community can contribute to an expeditious and life-saving intervention. Clinical Relevance: First responders who may interact with a young athlete have low knowledge of MH and its relationship to heat illness. Similar lack of awareness exists among hospital personnel who care for young individuals with heat illness. Educating the first responders about this condition can speed up the time to intervene and save lives. [ABSTRACT FROM AUTHOR]

Jiechu Wang,1– 3,&ast; Yao Yu,1,&ast; Ya Gao,1– 3,&ast; Tingting Wan,1– 3 Zhukai Cong,1– 3 Zhengqian Li,1– 3 Yang Zhou,1– 3 Xiaoxiao Wang,4 Luyang Feng,1– 3 Yongzheng Han,1– 3 Jing Zhang,1– 3 Yinyin Qu,1– 3 Xiangyang Guo1– 3 1Department of Anesthesiology, Peking University Third Hospital, Beijing, 100191, People’s Republic of China; 2Beijing Center of Quality Control and Improvement on Clinical Anesthesia, Peking University Third Hospital, Beijing, 100191, People’s Republic of China; 3Anesthesia and Perioperative Medicine Branch of China International Exchange and Promotive Association for Medical and Health Care (CPAM), Beijing, 100191, People’s Republic of China; 4Research Center for Clinical Epidemiology, Peking University Third Hospital, Beijing, 100191, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiangyang Guo; Yinyin Qu, Department of Anesthesiology, Peking University Third Hospital, North Garden Road 49, Haidian District, Beijing, 100191, People’s Republic of China, Email puthmzk@hsc.pku.edu.cn; quyinyin@bjmu.edu.cnBackground: Malignant hyperthermia (MH) is a hypermetabolic syndrome with high mortality rates. Early detection and prompt intravenous administration of dantrolene are crucial for effective management of MH. However, there is currently a lack of comprehensive nationwide surveys on the availability of dantrolene and anesthesiologists’ understanding of MH in China.Methods: A nationwide survey was conducted between January 2022 and June 2022. Online questionnaires on the cognition of MH among anesthesiologists in China were sent through social platforms to anesthesiologists in mainland China. Data regarding participants’ perception of MH-related knowledge, availability of domestic dantrolene, and reported MH cases were collected in this study.Results: Responses were collected from a total of 11,354 anesthesiologists representing 31 provinces across the Chinese mainland. Among the 11 scoring questions, the highest accuracy rates were observed for the question regarding therapeutic drugs for MH (99.3%) and the characteristics of MH (98.0%). Conversely, the question pertaining to the earliest clinical signs of MH had the lowest accuracy rate (23.5%). Significant variations were observed in the scores among different professional titles (P=0.003), academic degree (P< 0.001), hospital classification (P< 0.001), and urban hierarchy (P< 0.001). Of the respondents, 919 (8.1%) anesthesiologists reported dantrolene availability in their hospitals, and 631 (5.6%) indicated unclear. A total of 136 hospitals in this survey reported at least one previous case of MH.Conclusion: Mainland China faces challenges such as insufficient experience in diagnosing and treating MH, as well as difficulty in obtaining dantrolene. To improve the public awareness of MH, it is imperative to establish and promote a refined MH training system. Additionally, a streamlined and rapid dantrolene linkage emergency system should be implemented to ensure prompt access to the drug.Keywords: malignant hyperthermia, dantrolene, China, anesthesiologists, survey

The text discusses the opioid crisis in the United States, with over 106,000 fatal overdoses in 2021. The crisis disproportionately affects racial-ethnic minorities, with the per capita overdose mortality rate among non-Hispanic Black individuals more than tripled between 2010 and 2019. The role of internists in addressing the crisis is highlighted, emphasizing the importance of both structural and relational harm reduction approaches. The text provides an example of how an internist can incorporate harm reduction strategies in a patient encounter, despite limited access to structural resources. It concludes by urging internists to consider these approaches and advocating for a culture change and ownership of harm reduction in the healthcare system. [Extracted from the article]

Brown-Vialetto-Van Laere (BVVL) syndrome is a disease characterized by lower cranial nerve involvement, lower and upper motor neuron extremity findings, and sensorineural deafness. Respiratory failure (the most common non-neurological finding), muscle weakness, and slurred speech are other features. Less than 100 patients have been reported in Europe in the last century. Since it is a very rare disease, there is not enough data in the literature regarding the anesthesia approach. In motor neuron diseases, there is a risk of prolonged respiratory depression with general anesthesia because neuromuscular blocking drugs can increase paralysis and muscle weakness and residual neuromuscular block may occur. However, since the etiopathogenesis of BVVL syndrome remains unclear, our general anesthesia management in two different patients with BVVL syndrome is described. [ABSTRACT FROM AUTHOR]

Background: Patient safety is the reduction of risk of unnecessary harm associated with healthcare to an acceptable minimum. One of the outcomes frequently analysed in studies addressing this theme is the occurrence of adverse events. This study was conducted to assess anaesthesia related perioperative adverse events. Materials and Methods: This study comprised of 100 anaesthetic procedures in all. The subjects had been asked for consent. The adverse events were noticed. Statistical analysis had been conducted using SPSS software. Results: The most common adverse event was perioperative cardiac arrest observed in 29 subjects, followed by unexpected difficult airway seen in 16 subjects. Perioperative pulmonary aspiration was noticed 10 subjects. Stroke/coma was seen in 9 subjects and malignant hyperthermia was seen in 3 subjects. Total 67 complications had been observed. Conclusion: The most common perioperative complication was cardiac arrest followed by unexpected difficult airway. Other complications were pulmonary aspiration, stroke or coma, and malignant hyperthermia. [ABSTRACT FROM AUTHOR]