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Summary: The principles of environmentally sustainable healthcare as applied to anaesthesia and peri‐operative care are well documented. Associated recommendations focus on generic principles that can be applied to all areas of practice. These include reducing the use of inhalational anaesthetic agents and carbon dioxide equivalent emissions of modern peri‐operative care. However, four areas of practice have specific patient, surgical and anaesthetic factors that present barriers to the implementation of some of these principles, namely: neuroanaesthesia; obstetric; paediatric; and cardiac anaesthesia. This narrative review describes these factors and synthesises the available evidence to highlight areas of sustainable practice clinicians can address today, as well as posing several unanswered questions for the future. In neuroanaesthesia, improvements can be made by undertaking awake surgery, moving towards more reusables and embracing telemedicine in quaternary services. Obstetric anaesthesia continues to present questions regarding how services can move away from nitrous oxide use or limit its release to the environment. The focus for paediatric anaesthesia is addressing the barriers to total intravenous and regional anaesthesia. For cardiac anaesthesia, a significant emphasis is determining how to focus the substantial resources required on those who will benefit from cardiac interventions, rather than universal implementation. Whilst the landscape of evidence‐based sustainable practice is evolving, there remains an urgent need for further original evidence in healthcare sustainability targeting these four clinical areas. [ABSTRACT FROM AUTHOR]

This document is a response from the authors of a study on the impact of artificial intelligence (AI) arrhythmia mapping on various aspects of cardiac procedures. The authors address concerns raised by other researchers regarding the study's design and limitations. They acknowledge that the retrospective nature of the study may introduce unaccounted-for differences between the study patients and controls, but argue that it provided valuable early insights into the clinical benefits of AI. They also discuss the use of historical controls and the generalizability of the study's results. The authors conclude by emphasizing the need for prospective, randomized controlled trials to validate their findings. [Extracted from the article]

Syncope is a symptom in which transient loss of consciousness occurs as a consequence of a self-limited, spontaneously-terminating, period of cerebral hypoperfusion. Many circulatory disturbances (e.g. brady- or tachyarrhythmias, reflex cardioinhibition-vasodepression-hypotension) may trigger a syncope or near-syncope episode, and identifying the cause(s) is often challenging. Some syncope may involve multiple etiologies operating in concert, whereas in other cases multiple syncope events may be due to various differing causes at different times. In this communication we address current understanding of the principal contributors to syncope pathophysiology including examination of the manner in which concepts evolved, and an overview of factors that constitute consciousness and loss of consciousness, and aspects of neural-vascular control and communication that are impacted by cerebral hypo perfusion leading to syncope . Emphasis focuses on: 1) current understanding of the way transient systemic hypotension impacts brain blood flow and brain function, 2) the complexity and temporal sequence of vascular, humoral and cardiac factors that may accompany the most common causes of syncope, 3) the range of circumstances and disease states that may lead to syncope, and 4) clinical features associated with syncope and in particular the reflex syncope syndromes.

Background: Small infants experience a myriad of stimuli while in the Neonatal Intensive Care Unit (NICU), with many being painful or stressful experiences, although medically necessary., Purpose: To determine what is known about nonpharmacological developmental care interventions used in the NICU to mitigate procedural pain of infants born under 32 weeks gestation., Search/strategy: Five electronic databases were searched: Medline, CINAHL, Scopus, Embase and the Cochrane Library. The inclusion criteria were as follows: experimental and nonexperimental studies from all publication years with infants born at less than 32 weeks gestational age; peer-reviewed research articles studying nonpharmacological interventions such as skin-to-skin care, facilitated tucking, nonnutritive sucking, hand hugs, and swaddling; and English language articles. Our search yielded 1435 articles. After the elimination of 736 duplicates, a further 570 were deemed irrelevant based on their abstract/titles. Then, 124 full-text articles were analyzed with our inclusion and exclusion criteria., Findings: Twenty-seven studies were reviewed. Sucrose, facilitated tucking, pacifier, skin-to-skin care, and human milk appeared to lessen pain experienced during heel sticks, suctioning, nasogastric tube insertions, and echocardiograms. All nonpharmacological interventions failed to prove efficacious to adequately manage pain during retinopathy of prematurity (ROP) examinations., Implications for Practice: Evidence review demonstrates that healthcare practitioners should use nonpharmacological measures to help prevent pain from day-to-day procedures in the NICU including heel sticks, nasogastric tube insertions, suctioning, echocardiograms, and subcutaneous injections., Implications for Research: Future research is necessary to better understand and measure how pain is manifested by very small premature infants. Specific research on mitigating the pain of examinations for retinopathy of prematurity is also needed., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 by The National Association of Neonatal Nurses.)

Cardioneuroablation has emerged as a potential alternative to cardiac pacing in selected cases with vasovagal reflex syncope, extrinsic vagally induced sinus bradycardia-arrest or atrioventricular block. The technique was first introduced decades ago, and its use has risen over the past decade. However, as with any intervention, proper patient selection and technique are a prerequisite for a safe and effective use of cardioneuroablation therapy. This document aims to review and interpret available scientific evidence and provide a summary position on the topic., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: The BCR::ABL1 is a hallmark of chronic myeloid leukemia (CML) and is also found in acute lymphoblastic leukemia (ALL). Most genomic breaks on the BCR side occur in two regions - Major and minor - leading to p210 and p190 fusion proteins, respectively., Methods: By multiplex long-distance PCR or next-generation sequencing technology we characterized the BCR::ABL1 genomic fusion in 971 patients (adults and children, with CML and ALL: pediatric ALL: n = 353; pediatric CML: n = 197; adult ALL: n = 166; adult CML: n = 255 patients) and designed "Break-App" web tool to allow visualization and various analyses of the breakpoints. Pearson's Chi-Squared test, Kolmogorov-Smirnov test and logistic regression were used for statistical analyses., Results: Detailed analysis showed a non-random distribution of breaks in both BCR regions, whereas ABL1 breaks were distributed more evenly. However, we found a significant difference in the distribution of breaks between CML and ALL. We found no association of breakpoints with any type of interspersed repeats or DNA motifs. With a few exceptions, the primary structure of the fusions suggests non-homologous end joining being responsible for the BCR and ABL1 gene fusions. Analysis of reciprocal ABL1::BCR fusions in 453 patients showed mostly balanced translocations without major deletions or duplications., Conclusions: Taken together, our data suggest that physical colocalization and chromatin accessibility, which change with the developmental stage of the cell (hence the difference between ALL and CML), are more critical factors influencing breakpoint localization than presence of specific DNA motifs., (© 2024. The Author(s).)

Abstract: Pediatric B-cell precursor (BCP) lymphoblastic malignancies are neoplasms with manifestation either in the bone marrow or blood (BCP acute lymphoblastic leukemia [BCP-ALL]) or are less common in extramedullary tissue (BCP lymphoblastic lymphoma [BCP-LBL]). Although both presentations are similar in morphology and immunophenotype, molecular studies have been virtually restricted to BCP-ALL so far. The lack of molecular studies on BCP-LBL is due to its rarity and restriction on small, mostly formalin-fixed paraffin-embedded (FFPE) tissues. Here, to our knowledge, we present the first comprehensive mutational and transcriptional analysis of what we consider the largest BCP-LBL cohort described to date (n = 97). Whole-exome sequencing indicated a mutational spectrum of BCP-LBL, strikingly similar to that found in BCP-ALL. However, epigenetic modifiers were more frequently mutated in BCP-LBL, whereas BCP-ALL was more frequently affected by mutation in genes involved in B-cell development. Integrating copy number alterations, somatic mutations, and gene expression by RNA sequencing revealed that virtually all molecular subtypes originally defined in BCP-ALL are present in BCP-LBL, with only 7% of lymphomas that were not assigned to a subtype. Similar to BCP-ALL, the most frequent subtypes of BCP-LBL were high hyperdiploidy and ETV6::RUNX1. Tyrosine kinase/cytokine receptor rearrangements were detected in 7% of BCP-LBL. These results indicate that genetic subtypes can be identified in BCP-LBL using next-generation sequencing, even in FFPE tissue, and may be relevant to guide treatment., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Low-dose aspirin is an effective venous thromboembolism (VTE) prophylactic medication in primary total joint arthroplasty, but the efficacy and safety of the formulations of chewable and enteric-coated aspirin have not been compared. The purpose of this study was to investigate the VTE and gastrointestinal (GI) complication rates of chewable and enteric-coated 81 mg aspirin bis in die for VTE prophylaxis in primary total joint arthroplasty., Methods: A retrospective, single-institution cohort study was performed on patients who underwent primary total hip arthroplasty (THA) and total knee arthroplasty (TKA) from 2017 to 2021. Comparisons were made between 4,844 patients who received chewable, noncoated aspirin 81 mg and 4,388 patients who received enteric-coated 81 mg aspirin. Power analysis demonstrated 1,978 and 3,686 patients were needed per group to achieve a power of 80% for 90-day VTE rates (using inferiority testing) and GI complications (using superiority testing), respectively. Patients had similar baseline characteristics. Statistical analyses were done using t-tests and Chi-squared tests, with statistical significance defined as a P value < .05., Results: There were no significant differences in the incidences of postoperative VTE (0.31% versus 0.55%; P = .111) or GI complications (0.14% versus 0.14%; P = 1.000) between patients who received either chewable or enteric-coated 81 mg aspirin bis in die in the overall comparison that included both THA and TKA patients combined, or THA patients alone. However, the VTE incidence for TKA patients alone was significantly lower with chewable than enteric-coated aspirin (0.22% versus 0.62%; P = .037), with no difference in GI complications (0.13% versus 0.19%; P = .277)., Conclusions: Low-dose aspirin in enteric-coated formulation is inferior to chewable aspirin for VTE prophylaxis in primary TKA, but not inferior in THA patients. Both formulations have a similar GI complication rate. Therefore, it is reasonable to consider a transition from enteric-coated to uncoated chewable low-dose aspirin., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Cardiovascular autonomic dysfunction (CVAD) is a malfunction of the cardiovascular system caused by deranged autonomic control of circulatory homeostasis. CVAD is an important component of post-COVID-19 syndrome, also termed long COVID, and might affect one-third of highly symptomatic patients with COVID-19. The effects of CVAD can be seen at both the whole-body level, with impairment of heart rate and blood pressure control, and in specific body regions, typically manifesting as microvascular dysfunction. Many severely affected patients with long COVID meet the diagnostic criteria for two common presentations of CVAD: postural orthostatic tachycardia syndrome and inappropriate sinus tachycardia. CVAD can also manifest as disorders associated with hypotension, such as orthostatic or postprandial hypotension, and recurrent reflex syncope. Advances in research, accelerated by the COVID-19 pandemic, have identified new potential pathophysiological mechanisms, diagnostic methods and therapeutic targets in CVAD. For clinicians who daily see patients with CVAD, knowledge of its symptomatology, detection and appropriate management is more important than ever. In this Review, we define CVAD and its major forms that are encountered in post-COVID-19 syndrome, describe possible CVAD aetiologies, and discuss how CVAD, as a component of post-COVID-19 syndrome, can be diagnosed and managed. Moreover, we outline directions for future research to discover more efficient ways to cope with this prevalent and long-lasting condition., (© 2024. Springer Nature Limited.)

About 3 billion new tires are produced each year and about 800 million tires become waste annually. Global dependence upon tires produced from natural rubber and petroleum-based compounds represents a persistent and complex environmental problem with only partial and often-times, ineffective solutions. Tire emissions may be in the form of whole tires, tire particles, and chemical compounds, each of which is transported through various atmospheric, terrestrial, and aquatic routes in the natural and built environments. Production and use of tires generates multiple heavy metals, plastics, PAH's, and other compounds that can be toxic alone or as chemical cocktails. Used tires require storage space, are energy intensive to recycle, and generally have few post-wear uses that are not also potential sources of pollutants (e.g., crumb rubber, pavements, burning). Tire particles emitted during use are a major component of microplastics in urban runoff and a source of unique and highly potent toxic substances. Thus, tires represent a ubiquitous and complex pollutant that requires a comprehensive examination to develop effective management and remediation. We approach the issue of tire pollution holistically by examining the life cycle of tires across production, emissions, recycling, and disposal. In this paper, we synthesize recent research and data about the environmental and human health risks associated with the production, use, and disposal of tires and discuss gaps in our knowledge about fate and transport, as well as the toxicology of tire particles and chemical leachates. We examine potential management and remediation approaches for addressing exposure risks across the life cycle of tires. We consider tires as pollutants across three levels: tires in their whole state, as particulates, and as a mixture of chemical cocktails. Finally, we discuss information gaps in our understanding of tires as a pollutant and outline key questions to improve our knowledge and ability to manage and remediate tire pollution., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)

Introduction: Although two-stage exchange has been the standard of care for periprosthetic joint infection (PJI) in the United States, single-stage exchange is emerging as an option in select patients. The purpose of this study was to compare outcomes of patients undergoing single-stage and two-stage exchange using strict surgical indications., Methods: We reviewed a consecutive series of 196 patients with diagnosed PJI undergoing revision total knee and hip arthroplasty from 2017 to 2021. Patients were excluded if they had PJI history, plastic surgery coverage, or extensive bone loss requiring endoprosthesis. We compared the number of patients PJI-free at 1-year follow-up using MusculoSkeletal Infection Society criteria and patients requiring re-revision between the single-stage and two-stage groups., Results: In total, 126 patients met inclusion criteria. Of 61 knee patients (48.4%), 22 underwent single-stage (36%) and 39 underwent two-stage (63.9%). Of 65 hip patients (51.6%), 38 underwent single-stage (58.5%) and 27 underwent two-stage (41.5%). At a mean follow-up of 1.95 ± 0.88 years, a higher rate of knee patients were classified as having treatment success in the single-stage group (77.3% versus 69.2%, P = 0.501), however with comparable septic failure rates (18.1% single-stage versus 17.9% two-stage; P = 0.982). At a mean follow-up of 1.81 ± 0.9 years, a higher rate of hip patients were classified as having treatment success in the single-stage group (94.7% versus 81.5%, P = 0.089), and more patients had septic failures in the two-stage group (18.5% versus 5.3%; P = 0.089). No differences were observed in the microorganism profile. More total complications (P = 0.021) and mortalities were found in the single-stage knee cohort than in the two-stage cohort (22.7% versus 2.6%; P = 0.011)., Conclusion: Single-stage arthroplasty is a viable alternative to standard two-stage exchange in patients with PJI without a history of infection and with no bone or soft-tissue compromise. Additional studies with longer term follow-up are needed to evaluate its efficacy., (Copyright © 2024 by the American Academy of Orthopaedic Surgeons.)

Background: While patients who undergo both lumbar spinal fusion (LSF) and total hip arthroplasty (THA) have increased complication rates compared to patients who have not undergone LSF, there is a paucity of literature evaluating THA functional outcomes in patients with a history of LSF. This study was conducted to determine whether patients undergoing THA with a history of LSF have inferior functional outcomes compared to patients having no history of LSF., Methods: A retrospective matched case-control study was conducted at an academic center. Patients who underwent both THA and LSF (cases) were matched with controls who underwent THA without LSF. Inclusion criteria required a minimum of 1-year follow-up for the Hip Disability and Osteoarthritis Outcome Score Joint Replacement [HOOS-JR]. Following propensity matching for age, sex, race, body mass index, and comorbidities, 291 cases and 1,164 controls were included, with no demographic differences., Results: Patients who underwent both THA and LSF had a significantly lower preoperative HOOS-JR (47 versus 50; P < .001), postoperative HOOS-JR (77 versus 85; P < .001), a significant lower rate of achieving the patient acceptable symptom state (55 versus 67%; P < .001), with no significant difference in delta HOOS-JR (34 versus 34; P = .834). When comparing patients undergoing THA before LSF or LSF before THA, no differences existed for preoperative HOOS-JR (50 versus 47; P = .304), but patients undergoing THA before LSF had lower postoperative HOOS-JR scores (74 versus 81; P = .034), a lower-delta HOOS-JR (27 versus 35; P = .022), and a lower rate of reaching the HOOS-JR minimal clinically important difference (62 versus 76%; P = .031)., Conclusions: Patients who have a history of LSF experience a similar improvement in hip function when undergoing THA compared to patients who do not have a history of LSF. However, due to lower preoperative function, they may have a lower postoperative functional outcome ceiling. Additionally, patients undergoing THA before LSF have worse hip functional outcomes than patients undergoing LSF before THA., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aims: The pathophysiology of orthostatic hypotension (OH), a common clinical condition, associated with adverse outcomes, is incompletely understood. We examined the relationship between OH and circulating endostatin, an endogenous angiogenesis inhibitor with antitumour effects proposed to be involved in blood pressure (BP) regulation., Methods and Results: We compared endostatin levels in 146 patients with OH and 150 controls. A commercial chemiluminescence sandwich immunoassay was used to measure circulating levels of endostatin. Linear and multivariate logistic regressions were conducted to test the association between endostatin and OH. Endostatin levels were significantly higher in OH patients (59 024 ± 2513 pg/mL) vs. controls (44 090 ± 1978pg/mL, P < 0.001). A positive linear correlation existed between endostatin and the magnitude of systolic BP decline upon standing ( P < 0.001). Using multivariate analysis, endostatin was associated with OH (adjusted odds ratio per 10% increase of endostatin in the whole study population = 1.264, 95% confidence interval 1.141-1.402), regardless of age, sex, prevalent cancer, and cardiovascular disease, as well as traditional cardiovascular risk factors., Conclusion: Circulating endostatin is elevated in patients with OH and may serve as a potential clinical marker of increased cardiovascular risk in patients with OH. Our findings call for external validation. Further research is warranted to clarify the underlying pathophysiological mechanisms., Competing Interests: Conflict of interest: A.F. received speaker and consultation fees from Medtronic Inc., Finapres Medical Systems, and Bristol Myers Squibb. The remaining authors report no conflict of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Acute leukemia continues to be a major cause of death from disease worldwide and current chemotherapeutic agents are associated with significant morbidity in survivors. While better and safer treatments for acute leukemia are urgently needed, standard drug development pipelines are lengthy and drug repurposing therefore provides a promising approach. Our previous evaluation of FDA-approved drugs for their antileukemic activity identified disulfiram, used for the treatment of alcoholism, as a candidate hit compound. This study assessed the biological effects of disulfiram on leukemia cells and evaluated its potential as a treatment strategy. We found that disulfiram inhibits the viability of a diverse panel of acute lymphoblastic and myeloid leukemia cell lines (n = 16) and patient-derived xenograft cells from patients with poor outcome and treatment-resistant disease (n = 15). The drug induced oxidative stress and apoptosis in leukemia cells within hours of treatment and was able to potentiate the effects of daunorubicin, etoposide, topotecan, cytarabine, and mitoxantrone chemotherapy. Upon combining disulfiram with auranofin, a drug approved for the treatment of rheumatoid arthritis that was previously shown to exert antileukemic effects, strong and consistent synergy was observed across a diverse panel of acute leukemia cell lines, the mechanism of which was based on enhanced ROS induction. Acute leukemia cells were more sensitive to the cytotoxic activity of disulfiram than solid cancer cell lines and non-malignant cells. While disulfiram is currently under investigation in clinical trials for solid cancers, this study provides evidence for the potential of disulfiram for acute leukemia treatment. KEY MESSAGES: Disulfiram induces rapid apoptosis in leukemia cells by boosting oxidative stress. Disulfiram inhibits leukemia cell growth more potently than solid cancer cell growth. Disulfiram can enhance the antileukemic efficacy of chemotherapies. Disulfiram strongly synergises with auranofin in killing acute leukemia cells by ROS induction. We propose testing of disulfiram in clinical trial for patients with acute leukemia., (© 2024. The Author(s).)

There is a perceived need to express concisely the advice of guidelines in the context of consideration of invasive management of highly symptomatic vasovagal syncope. In response to this need the table is presented as a checklist and the text adds explanation and details. It is anticipated that this will prove to be of value for clinicians., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Tilt table testing (TTT) has been used for decades to study short-term blood pressure (BP) and heart rate regulation during orthostatic challenges. TTT provokes vasovagal reflex in many syncope patients as a background of widespread use. Despite the availability of evidence-based practice syncope guidelines, proper application and interpretation of TTT in the day-to-day care of syncope patients remain challenging. In this review, we offer practical information on what is needed to perform TTT, how results should be interpreted including the Vasovagal Syncope International Study classification, why syncope induction on TTT is necessary in patients with unexplained syncope and on indications for TTT in syncope patient care. The minimum requirements to perform TTT are a tilt table with an appropriate tilt-down time, a continuous beat-to-beat BP monitor with at least three electrocardiogram leads and trained staff. We emphasize that TTT remains a valuable asset that adds to history building but cannot replace it, and highlight the importance of recognition when TTT is abnormal even without syncope. Acknowledgement by the patient/eyewitness of the reproducibility of the induced attack is mandatory in concluding a diagnosis. TTT may be indicated when the initial syncope evaluation does not yield a certain, highly likely, or possible diagnosis, but raises clinical suspicion of (1) reflex syncope, (2) orthostatic hypotension (OH), (3) postural orthostatic tachycardia syndrome or (4) psychogenic pseudosyncope. A therapeutic indication for TTT in the patient with a certain, highly likely or possible diagnosis of reflex syncope, may be to educate patients on prodromes. In patients with reflex syncope with OH TTT can be therapeutic to recognize hypotensive symptoms causing near-syncope to perform physical countermanoeuvres for syncope prevention (biofeedback). Detection of hypotensive susceptibility requiring therapy is of special value., (© 2023 The Authors. Clinical Physiology and Functional Imaging published by John Wiley & Sons Ltd on behalf of Scandinavian Society of Clinical Physiology and Nuclear Medicine.)

Introduction: Physiology-guided cardiopulmonary resuscitation (CPR) offers the potential to optimize resuscitation and enable early prognosis., Methods: Physiology-Guided CPR was one of six focus topic for the Wolf Creek XVII Conference held on June 14-17, 2023 in Ann Arbor, Michigan, USA. International thought leaders and scientists in the field of cardiac arrest resuscitation from academia and industry were invited. Participants submitted via online survey knowledge gaps, barriers to translation and research priorities for each focus topic. Expert panels used the survey results and their own perspectives and insights to create and present a preliminary unranked list for each category, which was then debated, revised and ranked by all attendees to identify the top 5 for each category., Results: Top knowledge gaps include identifying optimal strategies for the evaluation of physiology-guided CPR and the optimal values for existing patients using patient outcomes. The main barriers to translation are the limited usability outside of critical care environments and the training and equipment required for monitoring. The top research priorities are the development of clinically feasible and reliable methods to continuously and non-invasively monitor physiology during CPR and prospective human studies proving targeting parameters during CPR improves outcomes., Conclusion: Physiology-guided CPR has the potential to provide individualized resuscitation and move away from a one-size-fits-all approach. Current understanding is limited, and clinical trials are lacking. Future developments need to consider the clinical application and applicability of measurement to all healthcare settings. Therefore, clinical trials using physiology-guided CPR for individualisation of resuscitation efforts are needed., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Janet Bray is an Associate Editor of Resuscitation Plus. Lars Wik is a medical advisor to Stryker Emergency Care and holds patents through his Hospital licenced to Stryker and Zoll., (© 2024 The Author(s).)