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Histones are conserved nuclear proteins that function as part of the nucleosome in the regulation of chromatin structure and gene expression. Interestingly, extracellular histones populate biofluids from healthy individuals, and when elevated, may contribute to various acute and chronic diseases. It is generally assumed that most extracellular histones exist as nucleosomes, as components of extracellular chromatin. We analysed cell culture models under normal and stressed conditions to identify pathways of histone secretion. We report that core and linker histones localize to extracellular vesicles (EVs) and are secreted via the multivesicular body/exosome pathway. Upregulation of EV histone secretion occurs in response to cellular stress, with enhanced vesicle secretion and a shift towards a population of smaller EVs. Most histones were membrane associated with the outer surface of EVs. Degradation of EV-DNA did not impact significantly on EV-histone association. Individual histones  and histone octamers bound strongly to liposomes and EVs, but nucleosomes did not, showing histones do not require DNA for EV binding. Histones colocalized to tetraspanin positive EVs but using genetic or pharmacological intervention, we found that all known pathways of exosome biogenesis acted positively on histone secretion. Inhibition of autophagy and lysosomal degradation had a strong positive effect on EV histone release. Unexpectedly, EV-associated histones lacked the extensive post-translational modification of their nuclear counterparts, suggesting loss of PTMs may be involved in their trafficking or secretion. Our data does not support a significant role for EV-histones existing as nucleosomes. We show for the first time that histones are secreted from cells as membrane proteins via EVs/exosomes. This fundamental discovery provides support for further investigation of the biological activity of exosome associated histones and their role in disease.

Background: Adequate cerebral perfusion is central during general anesthesia. However, perfusion is not readily measured bedside. Clinicians currently rely mainly on MAP as a surrogate even though the relationship between blood pressure and cerebral blood flow is not well understood. The aim of this study was to apply phase contrast MRI to characterize blood flow responses in healthy volunteers to commonly used pharmacological agents that increase or decrease arterial blood pressure.

Methods: Eighteen healthy volunteers aged 30-50 years were investigated with phase contrast MRI. Intraarterial blood pressure monitoring was used. First, intravenous noradrenaline was administered to a target MAP of 20% above baseline. After a wash-out period, intravenous labetalol was given to a target MAP of 15% below baseline. Cerebral blood flow was measured using phase contrast MRI and defined as the sum of flow in the internal carotid arteries and vertebral arteries. CO was defined as the flow in the ascending aorta.

Baseline median cerebral blood flow was 772 ml/min (interquartile range, 674 to 871), and CO was 5,874 ml/min (5,199 to 6,355). The median dose of noradrenaline was 0.17 µg · kg⁻¹ · h⁻¹ (0.14 to 0.22). During noradrenaline infusion, cerebral blood flow decreased to 705 ml/min (606 to 748; P = 0.001), and CO decreased to 4,995 ml/min (4,705 to 5,635; P = 0.01). A median dose of labetalol was 120 mg (118 to 150). After labetalol boluses, cerebral blood flow was unchanged at 769 ml/min (734 to 900; P = 0.68). CO increased to 6,413 ml/min (6,056 to 7,464; P = 0.03).

Conclusion: In healthy awake subjects, increasing MAP using intravenous noradrenaline decreased cerebral blood flow and CO. This data does not support inducing hypertension with noradrenaline to increase cerebral blood flow. Cerebral blood flow was unchanged when decreasing MAP using labetalol.

Background: The risk of high-energy trauma injuries on construction sites is relatively high. A delayed response time could affect outcomes after severe injury. This study assessed if an advanced first aid course for first aid response for laypersons (employees or apprentices) in the construction industry or real-time video communication and support with ambulance personnel, or neither, together with access to an advanced medical kit, would have an effect on immediate layperson vital responses in a severe injury scenario.

Method: This was a controlled simulation study. Employees or apprentices at a construction site were recruited and randomly allocated into a group with video support or not, and advanced first aid course or not, and where one group had both. The primary outcomes were correct behavior to recognize and manage an occluded airway and correct behavior to stop life-threatening bleeding from a lower extremity injury. Secondary outcomes included head-to-toe assessment performed, placement of a pelvic sling, and application of remote vital signs monitors.

Results: Ninety participants were included in 10 groups of 3 for each of 4 exposures. One group was tested first as a baseline group, and then later after having done the training course. Live video support was effective in controlling bleeding. A first aid course given beforehand did not seem to be as effective on controlling bleeding. Video support and the first aid course previously given improved the ability of bystanders to manage the airway, the combination of the two being no better than each of the interventions taken in isolation. Course exposure and video support together were not superior to the course by itself or video by itself, except regarding placing the biosensors on the injured after video support. Secondary results showed an association between video support and completing a head-to-toe assessment. Both interventions were associated with applying a pelvic sling.

Conclusion: These findings show that laypersons, here construction industry employees, can be supported to achieve good performance as first responders in a major injury scenario. Prior training, but especially live video support without prior training, improves layperson performance in this setting.

BACKGROUND: Patient safety is fundamental when providing care in the operating room. Still, adverse events and errors are a challenge for patient safety worldwide. To avoid preventable patient harm, organisations need a positive safety culture, the measurable component of which is known as the safety climate. To best improve the safety climate the current attitudes to safety must first be understood.

AIM: To explore operating room nurses' safety attitudes and their views on how to improve patient safety in operating rooms.

ETHOD: A cross-sectional study using the Swedish-translated version of the Safety Attitudes Questionnaire, Operating Room version. Data were collected using an online survey platform.

RESULTS: 358 operating room nurses completed the questionnaire. The results show that the older age group rated their working conditions and management support as better than the younger age groups. The older age group also rated their stress recognition as lower compared with the younger age groups. The same pattern was seen in terms of work experience, with more-experienced respondents showing a higher mean score for the factor working conditions and a lower mean score for the factor stress recognition as compared with their less-experienced colleagues. When comparing hospital types, county hospital employees had higher factor scores for safety climate, job satisfaction and working conditions than university hospital employees. The respondents' most recurring recommendations for improving patient safety were 'Having better and clearer communication' followed by 'Having enough time to do things the way they should be done'.

CONCLUSION: More focus on safety with increasing age and experience was observed in this cohort. Need for improvements is reported for patient safety in operating rooms, mainly when it comes to communication and workload. To improve and develop patient safety in the operating room, the organisational safety climate needs to be actively managed and developed. One step in actively managing the safety climate may be efforts to retain experienced operating room nurses.

Aim: To identify, define and achieve consensus on perioperative patient safety indicators within a Swedish context.

Design: A modified Delphi method.

Methods: A purposeful sample of 22 experts, all experienced operating room nurse specialists, was recruited for this study. A questionnaire was constructed incorporating statements derived from a preceding study. The experts were asked to rate the importance of each statement concerning patient safety during the perioperative phase. The data collection occurred through an online survey platform between November 2022 and April 2023. The CREDES checklist guided the reporting of this study.

Results: The three-round Delphi study resulted in consensus on 73 statements out of 103, encompassing 74% process indicators and 26% structure indicators. Key areas of consensus included the use of the Surgical Safety Checklist and optimizing the operating room environment.

Conclusion: Consensus was reached on perioperative safety indicators, underscoring the intricate challenges involved in ensuring patient safety in the operating room. It emphasizes the important integration of both structure and process indicators for comprehensive safety assessment during surgical procedures. Recognizing the difficulty in measuring factors like teamwork and communication, essential for patient safety, the study offers practical guidance. It underlines a balanced approach and specific consensus areas applicable in clinical practice to enhance perioperative patient safety.

Implications for the profession and patient care:This study provides concrete practice guidance and establishes a structured framework for evaluating perioperative care processes. It emphasizes the critical role of professionals having the necessary skills and being present during surgical procedures. Additionally, the study underscores the paramount importance of effective communication and teamwork within the operating room team, substantively contributing to overall patient safety enhancement.

Impact: The study focused on addressing the challenge of ensuring patient safety in operating rooms, acknowledging the persistent complications related to surgery despite global efforts to eliminate avoidable harm in healthcare. Consensus was reached on 73 crucial indicators for perioperative patient safety, emphasizing a balanced approach integrating both process and structure indicators for a comprehensive assessment of safety during surgical procedures. The study has a broad impact on professionals and healthcare systems, providing concrete guidance for practice and offering a structured process for evaluating perioperative care.

Reporting Method: The study is reported informed by 'Guidance on Conducting and REporting DElphi Studies (CREDES) in palliative care: Recommendations derived from a methodological systematic review'.

Patient or Public Contribution: No patient or public contribution.

BACKGROUND: Cardiac mechanics are influenced by loading conditions as well as sympathetic tone. Left atrial (LA) contractile function assessed by two-dimensional (2D) strain has been described in the setting of controlled preload alterations; however, studies show conflicting findings about change or direction of change. We hypothesized that the controlled preload reduction and the sympathetic nervous system activation that occurs during a standardized Valsalva manoeuvre would bring about a change in LA contraction strain.a

METHODS: Healthy young adults of both sexes were recruited. Transthoracic echocardiographic ultrasound images were collected before and during a Valsalva manoeuvre. Standard imaging windows for LA strain assessment were used and the images were copied and stored for later offline analysis. These were assessed for adequate atrial wall visualization in 2D strain assessment. Paired comparisons were carried out using Student's T test.

RESULT: Thirty-eight participants were included and there were 22 complete studies with paired pre- and during Valsalva manoeuvre. LA contraction strain at baseline was 10.5 ± 2.8% (standard deviation) and during the Valsalva manoeuvre 10.6 ± 4.6%, p = 0.86.

CONCLUSION: The Valsalva manoeuvre, a combination of preload reduction and sympathetic nervous system activation, seems not to be associated with a change in LA contraction strain in healthy young individuals. LA contraction strain should be interpreted in the context of both atrial loading conditions and prevailing autonomic nervous system activity.

Background: Anesthesia preinduction anxiety in children can according to some studies lead to long-term anxiety and negative behavioral changes (NBC), while other studies have not found this effect. This secondary analysis from a recent premedication trial comparing clonidine and midazolam aimed to test the relation between preoperative anxiety assessed with modified Yale Preoperative Anxiety Scale (mYPAS) and postoperative NBCs assessed with Post Hospital Behavior Questionnaire (PHBQ), regardless of premedication type.

Methods: This is a planned secondary analysis from a published premedication comparison trial in an outpatient surgery cohort, children aged 2–7 years. Participant and preoperative factors, particularly preoperative anxiety as mYPAS scores, were assessed for association with development of postoperative NBCs.

Results: Fifty-four of the 115 participants had high preinduction anxiety (mYPAS >30), and 19 of 115 developed >3 postoperative NBCs 1 week after surgery. There was no association between preinduction anxiety level as mYPAS scores and the development of postoperative NBCs at 1 week after surgery (10 of 19 had both, p =.62) nor after 4- or 26-weeks post-surgery. Only lower age was associated with development of NBCs postoperatively.

Conclusions: Based on the findings from this cohort, high preinduction anxiety does not appear to be associated with NBCs postoperatively in children premedicated with clonidine or midazolam.

Anastomotic defect (AD) after esophagectomy can lead to severe complications with need for surgical or endoscopic intervention. Early detection enables early treatment and can limit the consequences of the AD. As of today, there are limited methods to predict AD. In this study, we have used microdialysis (MD) to measure local metabolism at the intrathoracic anastomosis. Feasibility and possible diagnostic use were investigated. Sixty patients planned for Ivor Lewis esophagectomy were enrolled. After construction of the anastomosis, surface MD (S-MD) probes were attached to the outer surface of the esophageal remnant and the gastric conduit in close vicinity of the anastomosis and left in place for 7 postoperative days (PODs). Continuous sampling of local tissue concentrations of metabolic substances (glucose, lactate, and pyruvate) was performed postoperatively. Outcome, defined as AD or not according to Esophagectomy Complications Consensus Group definitions, was recorded at discharge or at first postoperative follow up. Difference in concentrations of metabolic substances was analyzed retrospectively between the two groups by means of artificial neural network technique. S-MD probes can be attached and removed from the gastric tube reconstruction without any adverse events. Deviating metabolite concentrations on POD 1 were associated with later development of AD. In subjects who developed AD, no difference in metabolic concentrations between the esophageal and the gastric probe was recorded. The technical failure rate of the MD probes/procedure was high. S-MD can be used in a clinical setting after Ivor Lewis esophagectomy. Deviation in local tissue metabolism on POD 1 seems to be associated with development of AD. Further development of MD probes and procedure is required to reduce technical failure.