Myopathic manifestations across the adult lifespan of patients with malignant hyperthermia susceptibility: a narrative review.

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.

An Association between OXPHOS-Related Gene Expression and Malignant Hyperthermia Susceptibility in Human Skeletal Muscle Biopsies.

Malignant hyperthermia (MH) is a pharmacogenetic condition of skeletal muscle that manifests in hypermetabolic responses upon exposure to volatile anaesthetics. This condition is caused primarily by pathogenic variants in the calcium-release channel RYR1, which disrupts calcium signalling in skeletal muscle. However, our understanding of MH genetics is incomplete, with no variant identified in a significant number of cases and considerable phenotype diversity.

Pholcodine and allergy to neuromuscular blocking agents: where are we and how did we get here?

Despite the purported link between pholcodine and neuromuscular blocking agent allergy, screening for prior pholcodine use offers no practical benefit to patients, and anaesthetists should continue to use a neuromuscular blocking agent where this is clinically indicated.

Comparison of Transcriptomic Changes in Survivors of Exertional Heat Illness with Malignant Hyperthermia Susceptible Patients.

Exertional heat illness (EHI) is an occupational health hazard for athletes and military personnel-characterised by the inability to thermoregulate during exercise. The ability to thermoregulate can be studied using a standardised heat tolerance test (HTT) developed by The Institute of Naval Medicine. In this study, we investigated whole blood gene expression (at baseline, 2 h post-HTT and 24 h post-HTT) in male subjects with either a history of EHI or known susceptibility to malignant hyperthermia (MHS): a pharmacogenetic condition with similar clinical phenotype.

Peripheral regional anaesthesia and outcomes: a narrative review of the literature from 2013 to 2023.

The use of peripheral regional anaesthesia continues to increase, yet the evidence supporting its use and impact on relevant outcomes often lacks scientific rigour, especially when considering the use of specific blocks for a particular surgical indication. In this narrative review, we consider the relevant literature in a 10-yr period from 2013. We performed a literature search (MEDLINE and EMBASE) for articles reporting randomised controlled trials and other comparative trials of peripheral regional anaesthetic blocks vs systemic analgesia in adult patients undergoing surgery.

COVID-19-associated pulmonary aspergillosis in mechanically ventilated patients: a prospective, multicentre UK study.

Background: Invasive pulmonary aspergillosis is a complication of severe COVID-19, with regional variation in reported incidence and mortality. We describe the incidence, risk factors and mortality associated with COVID-19-associated pulmonary aspergillosis (CAPA) in a prospective, multicentre UK cohort.

Methods: From March 2020 to March 2021, 266 mechanically ventilated adults with COVID-19 were enrolled across 5 UK hospital intensive care units (ICUs).

Putative malignant hyperthermia mutation Ca1.1-R174W is insufficient to trigger a fulminant response to halothane or confer heat stress intolerance.

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.

Suspected perioperative anaphylaxis: are we making the correct diagnosis?

We provide a commentary on aspects of a prospective study of the epidemiology of perioperative anaphylaxis in Japan (Japanese Epidemiologic Study for Perioperative Anaphylaxis [JESPA]). Accurate diagnosis of perioperative anaphylaxis is important for research but essential for clinical safety. We evaluate the diagnostic approach used in the JESPA study and caution against over-reliance on diagnostic tests that lack sensitivity and specificity when clinical data suggest an immediate perioperative hypersensitivity reaction is likely.

What is malignant hyperthermia susceptibility?

The molecular mechanisms of susceptibility to malignant hyperthermia are complex. The malignant hyperthermia susceptibility phenotype should be reserved for patients who have a personal or family history consistent with malignant hyperthermia under anaesthesia and are subsequently demonstrated through diagnostic testing to be at risk.

Electropolishing of Aluminum at Room Temperature Using a Green DES of Choline Chloride and Propylene Glycol.

For applications of aluminum where the smoothness or reflectivity of the aluminum matters, electropolishing is necessary to polish the aluminum surface sufficiently. This electropolishing is traditionally done with hazardous solutions in non-ideal conditions, such as low-temperature perchloric acid-ethanol mixtures. Here, we describe electropolishing of aluminum using a deep eutectic system composed of propylene glycol and choline chloride, with polishing accomplished at room temperature and using an inexpensive apparatus.

Serial image interpretation tasks improve accuracy and increase confidence in Level 1 echocardiography reporting: a pilot study.

Background: Focused echocardiography is increasingly used in acute and emergency care, with point-of-care ultrasound integrated into several specialist training curricula (e.g. Emergency Medicine, Cardiology, Critical Care).

Functional analysis of RYR1 variants in patients with confirmed susceptibility to malignant hyperthermia.

Background: A major bottleneck to the introduction of noninvasive presymptomatic diagnostic tests for the pharmacogenetic disorder malignant hyperthermia is the lack of functional data for associated variants.

Methods: We screened 50 genes having a potential role in skeletal muscle calcium homeostasis using the HaloPlex™ (Agilent Technologies, Santa Clara, CA, USA) target enrichment system and next-generation sequencing. Twenty-one patients with a history of a clinical malignant hyperthermia reaction together with a positive in vitro contracture test were included.

Processed Electroencephalogram-Based Monitoring to Guide Sedation in Critically Ill Adult Patients: Recommendations from an International Expert Panel-Based Consensus.

Background: The use of processed electroencephalography (pEEG) for depth of sedation (DOS) monitoring is increasing in anesthesia; however, how to use of this type of monitoring for critical care adult patients within the intensive care unit (ICU) remains unclear.

Methods: A multidisciplinary panel of international experts consisting of 21 clinicians involved in monitoring DOS in ICU patients was carefully selected on the basis of their expertise in neurocritical care and neuroanesthesiology. Panelists were assigned four domains (techniques for electroencephalography [EEG] monitoring, patient selection, use of the EEG monitors, competency, and training the principles of pEEG monitoring) from which a list of questions and statements was created to be addressed.

Variants in ASPH cause exertional heat illness and are associated with malignant hyperthermia susceptibility.

Exertional heat illness (EHI) and malignant hyperthermia (MH) are life threatening conditions associated with muscle breakdown in the setting of triggering factors including volatile anesthetics, exercise, and high environmental temperature. To identify new genetic variants that predispose to EHI and/or MH, we performed genomic sequencing on a cohort with EHI/MH and/or abnormal caffeine-halothane contracture test. In five individuals, we identified rare, pathogenic heterozygous variants in ASPH, a gene encoding junctin, a regulator of excitation-contraction coupling.

Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses.

The role of immune responses to previously seen endemic coronavirus epitopes in severe acute respiratory coronavirus 2 (SARS-CoV-2) infection and disease progression has not yet been determined. Here, we show that a key characteristic of fatal outcomes with coronavirus disease 2019 (COVID-19) is that the immune response to the SARS-CoV-2 spike protein is enriched for antibodies directed against epitopes shared with endemic beta-coronaviruses and has a lower proportion of antibodies targeting the more protective variable regions of the spike. The magnitude of antibody responses to the SARS-CoV-2 full-length spike protein, its domains and subunits, and the SARS-CoV-2 nucleocapsid also correlated strongly with responses to the endemic beta-coronavirus spike proteins in individuals admitted to an intensive care unit (ICU) with fatal COVID-19 outcomes, but not in individuals with nonfatal outcomes.

: a new open access journal for anaesthesiology, critical care, and pain medicine.

is a new open access journal to complement . This editorial describes the rationale for the journal and the breadth of content it is seeking to attract. As with other BJA titles, conforms to the highest standards of editorial and publication practice, and it aims to provide sector-leading author experience combined with reliable peer-reviewed content for the reader.

Ryanodine receptor leak triggers fiber Ca redistribution to preserve force and elevate basal metabolism in skeletal muscle.

Muscle contraction depends on tightly regulated Ca release. Aberrant Ca leak through ryanodine receptor 1 (RyR1) on the sarcoplasmic reticulum (SR) membrane can lead to heatstroke and malignant hyperthermia (MH) susceptibility, as well as severe myopathy. However, the mechanism by which Ca leak drives these pathologies is unknown.

Epidemiology of perioperative anaphylaxis in the United States: new insights but more to learn and do.

Gonzalez-Estrada and colleagues report an estimated risk of severe or fatal perioperative anaphylaxis of one in 6,825 procedures during the period 2005-2014. This is slightly higher than that reported previously in France and England. Several predictors of near-fatal and fatal reactions are identified, such as increased age, cancer, and congestive cardiac failure.

Mapping the impact of ICU design on patients, families and the ICU team: A scoping review.

Purpose: Scoping review to map outcomes and describe effects of intensive care unit (ICU) design features on patients, family, and healthcare professionals (HCPs).

Materials And Methods: Iteratively developed search strategy executed across seven databases. We included studies (January 2007 to May 2020) exploring ICU design features using any study design.

Identification of immune correlates of fatal outcomes in critically ill COVID-19 patients.

Prior studies have demonstrated that immunologic dysfunction underpins severe illness in COVID-19 patients, but have lacked an in-depth analysis of the immunologic drivers of death in the most critically ill patients. We performed immunophenotyping of viral antigen-specific and unconventional T cell responses, neutralizing antibodies, and serum proteins in critically ill patients with SARS-CoV-2 infection, using influenza infection, SARS-CoV-2-convalescent health care workers, and healthy adults as controls. We identify mucosal-associated invariant T (MAIT) cell activation as an independent and significant predictor of death in COVID-19 (HR = 5.

Prospective observational study to examine health-related quality of life and develop models to predict long-term patient-reported outcomes 6 months after hospital discharge with blunt thoracic injuries.

Objective: This study aimed to examine the long-term outcomes and health-related quality of life in patients with blunt thoracic injuries over 6 months from hospital discharge and develop models to predict long-term patient-reported outcomes.

Design: A prospective observational study using longitudinal survey design.

Setting: The study recruitment was undertaken at 12 UK hospitals which represented diverse geographical locations and covered urban, suburban and rural areas across England and Wales.