Sepsis is a dysregulated host response to severe infections, and immune dysfunction plays a crucial role in its pathogenesis. Elderly patients, a special population influenced by immunosenescence, are more susceptible to sepsis and have a worse prognosis. However, the immunopathogenic mechanisms underlying sepsis in elderly patients remain unclear. Here, we performed single-cell RNA sequencing of peripheral blood samples from young and old subjects and patients with sepsis. By exploring the transcriptional profiles of immune cells, we analyzed immune cell compositions, phenotype shifts, expression heterogeneities, and intercellular communication. In elderly patients with sepsis, innate immune cells (e.g., monocytes and DCs) exhibit decreased antigen presentation, presenting an overactive inflammatory and senescent phenotype. However, the immunophenotype of T cells shifted to characterize effector, memory, and exhaustion. Moreover, we identified strong interferon-γ responses of T cells in both aging and sepsis groups and a deranged inflammaging status in elderly sepsis patients. Tregs in elderly patients with sepsis showed increased abundance and enhanced immunosuppressive effects. In addition, metabolism-associated pathways were upregulated in T cells in elderly patients with sepsis, and the lysine metabolism pathway was enriched in Tregs. Cell-cell interaction analysis showed that the expression profile of ligand-receptor pairs was probably associated with aggravated immune dysfunction in elderly patients with sepsis. A novel HLA-KIR interaction was observed between Tregs and CD8 + T cells. These findings illustrate the immunological hallmarks of sepsis in elderly patients, and highlight that immunosuppressive and metabolic regulatory pathways may undergo important alterations in elderly patients with sepsis.

OBJECTIVE: Systematic evaluation of the safety of del Nido cardioplegia compared to cold blood cardioplegia in adult cardiac surgery.
METHODS: We systematically searched PubMed, EMbase, The Cochrane Library and ClinicalTrials.gov for randomized clinical trials (published by 14 January 2024) comparing del Nido cardioplegia to cold blood cardioplegia in adult. Our main endpoints were myocardial injury markers and clinical outcomes. We assessed pooled data by use of a random-effects model or a fixed-effects model.
RESULTS: A total of 10 studies were identified, incorporating 889 patients who received del Nido cardioplegia and 907 patients who received cold blood cardioplegia. The meta-analysis results showed that compared with the cold blood cardioplegia, the del Nido cardioplegia had less volume of cardioplegia, higher rate of spontaneous rhythm recovery after cross clamp release, lower levels of postoperative cardiac troponin T and creatinine kinase-myocardial band, all of which were statistically significant. However, there was no statistically significant difference in postoperative troponin I and postoperative left ventricular ejection fraction. The clinical outcomes including mechanical ventilation time, intensive care unit stay time, hospital stay time, postoperative stroke, postoperative new-onset atrial fibrillation, postoperative heart failure requiring intra-aortic balloon pump mechanical circulation support, and in-hospital mortality of both are comparable.
CONCLUSIONS: Existing evidence suggests that del Nido cardioplegia reduced volume of cardioplegia administration and attempts of defibrillation. The superior postoperative results in CTnT and CK-MB may provide a direction for further research on improvement of the composition of cardioplegia.

BACKGROUND: There is a high incidence of pulmonary atelectasis during paediatric laparoscopic surgeries. The authors hypothesised that utilising a recruitment manoeuvre or using continuous positive airway pressure may prevent atelectasis compared to conventional ventilation.
OBJECTIVE: The primary objective was to compare the degree of lung atelectasis diagnosed by lung ultrasound (LUS) using three different ventilation techniques in children undergoing laparoscopic surgeries.
METHODS: Randomised, prospective three-arm trial.
METHODS: Single institute, tertiary care, teaching hospital.
METHODS: Children of ASA PS 1 and 2 up to the age of 10 years undergoing laparoscopic surgery with pneumoperitoneum lasting for more than 30 min.
METHODS: Random allocation to one of the three study groups: CG group: Inspiratory pressure adjusted to achieve a TV of 5-8 ml/kg, PEEP of 5 cm H2O, respiratory rate adjusted to maintain end-tidal carbon dioxide (ETCO2) between 30-40 mm Hg with manual ventilation and no PEEP at induction. RM group: A recruitment manoeuvre of providing a constant pressure of 30 cm H2O for ten seconds following intubation was applied. A PEEP of 10 cm H2O was maintained intraoperatively. CPAP group: Intraoperative maintenance with PEEP 10 cm H2O with CPAP of 10 cm H2O at induction using mechanical ventilation was done.
METHODS: Lung atelectasis score at closure assessed by LUS.
RESULTS: Post induction, LUS was comparable in all three groups. At the time of closure, the LUS for the RM group (8.6 ± 4.9) and the CPAP group (8.8 ± 6.8) were significantly lower (p < 0.05) than the CG group (13.3 ± 3.8). In CG and CPAP groups, the score at closure was significantly higher than post-induction. The PaO2/FiO2 ratio was significantly higher (p < 0.05) for the RM group (437.1 ± 44.9) and CPAP group (421.6 ± 57.5) than the CG group (361.3 ± 59.4) at the time of pneumoperitoneum.
CONCLUSIONS: Application of a recruitment manoeuvre post-intubation or CPAP during induction and maintenance with a high PEEP leads to less atelectasis than conventional ventilation during laparoscopic surgery in paediatric patients.
BACKGROUND: CTRI/2019/08/02058.

BACKGROUND: Despite emerging evidence linking blood cell indices (BCIs) to sepsis mortality, the inconsistency of observational studies obscures the clarity of these associations. This study aims to clarify the causal influence of BCIs on 28-day mortality rates in sepsis patients.
METHODS: Utilizing univariable and multivariable Mendelian randomization (MR) analyses, we examined the impact of BCIs on sepsis mortality by analyzing data from extensive genome-wide association studies. The inverse-variance weighted (IVW) method was our primary analytic tool, complemented by several robustness checks to mitigate pleiotropy, including weighted median, mode-based estimates, MR-Egger regression, and MR-PRESSO. Subsequently, we conducted a retrospective study to further explore the correlation between platelet indices and 28-day mortality of sepsis using real-world data.
RESULTS: Our findings highlight a significant causal relationship between platelet distribution width (PDW) and 28-day mortality in sepsis, with the univariable Mendelian randomization approach yielding an odds ratio of 1.12 (95% CI, 1.06-1.26; P < 0.05). Multivariable analysis further substantiated PDW\'s robust association with mortality risk (OR 1.23; 95% CI, 1.03-1.48; P < 0.05). Conversely, our analysis did not uncover significant correlations between the genetic predispositions to other BCIs-including red blood cell count, erythrocyte distribution width, platelet count, mean platelet volume, white blood cell count, neutrophil count, neutrophil percentage, lymphocyte count, and lymphocyte percentage-and 28-day mortality in sepsis. Additionally, an inverse MR analysis did not establish a causal impact of 28-day mortality in sepsis on PDW (OR 1.00; 95% CI, 1.00-1.07; P = 0.29). Moreover, a similar result was observed in the retrospective study.
CONCLUSIONS: The study underscores the independent causal role of PDW in predicting 28-day mortality in sepsis, suggesting its potential utility in early patient assessment, risk stratification, and tailoring of therapeutic interventions.

Simulation is an effective training method for neonatal resuscitation (NR). However, the limitations brought about by the COVID-19 pandemic, and other resource constraints, have necessitated exploring alternatives. Virtual reality (VR), particularly 360-degree VR videos, have gained attraction in medical training due to their immersive qualities. The primary objectives of the study were to produce a high quality 360-degree virtual reality (VR) video capturing NR simulation and to determine if it could be an acceptable adjunct to teach NR. The secondary objective was to determine which aspects of NR could benefit from the incorporation of such a video in training. This was an exploratory development study. The first part consisted of producing the video using a GoPro action camera, Adobe Premiere Pro, and Unity Editor. In the second part participants were recruited, based on level of experience, to watch the video and answer questionnaires to determine acceptability (user experience and cognitive load) and aspects of NR which could benefit from the video. The video was successfully developed. Forty-six participants showed a strong general appreciation. User experience revealed high means (> 6) in the positive subscales and low means (< 4) for immersion side effect, with no difference between groups. Cognitive load was higher than anticipated. Participants indicated that this video could be effective for teaching crisis resource management principles, human and environment interactions, and procedural skills. The 360-degree VR video could be a potential new simulation adjunct for NR. Future studies are needed to evaluate learning outcomes of such videos.

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OBJECTIVE: Norepinephrine is available commercially in solution containing its salt (eg, tartrate), but only the base form (ie, norepinephrine base) is active pharmacologically. Unfortunately, the outer label of drug packages frequently reports the dosage of norepinephrine as a salt, which can lead potentially to therapeutic errors when prescribing norepinephrine. We performed a survey to assess the level of awareness of this issue.
METHODS: National survey.
METHODS: Acute care units of Italian hospitals.
METHODS: Acute care physicians and nurses.
METHODS: A 15-item online survey was emailed to 305 critical care practitioners in Italy. Questions included information on the participants\' background, methods of diluting norepinephrine, interpretation of recommended doses from guidelines, and a sample case related to the preparation and administration of the drug.
RESULTS: We collected 106 responses from 54 hospitals. All hospitals used norepinephrine bitartrate salt. Of the participants, 53% responded that the guidelines express norepinephrine dosages as a salt, 23% as the base form, and 24% were unsure or unaware about it. The simulated patient-dose calculation was resolved in 81% of cases with an incorrect calculation referring to the norepinephrine salt and only in 19% referring to the norepinephrine base.
CONCLUSIONS: There is significant variability in dosage management of norepinephrine across different hospital units, as well as a lack of knowledge regarding the salt-to-base ratio. Scientific publications (eg, guidelines) should specify whether they are referring to the base or salt form of norepinephrine. The adoption of different labeling and national standards for dilution may decrease the risk of therapeutic errors.

OBJECTIVE: To explore students\' and facilitators\' experiences of using a developed digital activity for interprofessional learning (IPL) focusing on critically ill patient handovers from a primary healthcare (PHC) centre to the ambulance service.
METHODS: A qualitative study design was employed, and the reporting of this study adheres to the Consolidated criteria for Reporting Qualitative research guidelines for qualitative studies.
METHODS: A PHC centre and the ambulance service in Stockholm, Sweden.
METHODS: A total of 31 participants were included in the study: 22 students from five different healthcare professions, seven facilitators and two observers.
METHODS: A digital IPL activity was developed to overcome geographical distances, and the scenario included the handover of a critically ill patient from personnel within the PHC centre to the ambulance service personnel for transport to an emergency department. Four digital IPL activities were conducted in 2021.
RESULTS: The digital IPL activity eliminated the issue of geographical distance for students and facilitators, and it enabled the students to find an interprofessional model for collaboration through reasoning, by communicating and sharing knowledge with the support of a common structure. Participants perceived the digital IPL activity and scenario as authentic, feasible and facilitated IPL. Using a case with an acute and life-threatening condition was a success factor for students to experience high realism in their IPL on patient safety, handover, care and treatment.
CONCLUSIONS: The developed digital IPL activity facilitated the students\' IPL and demonstrated potential sustainability as the digital approach supported overcoming geographical distances for both students and facilitators. By using a scenario involving an authentic case focusing on handovers of a critically ill patient, IPL, feasibility and acceptability were supported. However, it is crucial to emphasise that a comprehensive evaluation, both quantitative and qualitative, over an extended period of clinical rotations and involving a larger group of students is still warranted to ensure continuous improvement and development.

OBJECTIVE: To identify determinants of puerperal sepsis among postpartum women attending East Shoa Zone public hospitals, Central Ethiopia, 2023.
METHODS: An institutional-based, unmatched case-control study was conducted from 19 June 2023 to 4 September 2023, in East Shoa Zone public hospitals.
METHODS: 495 postpartum women (100 cases and 395 controls) were selected using systematic sampling techniques. Data were collected through face-to-face interviews and from medical charts using a pretested, structured questionnaire. The AOR with its corresponding 95% CI was used to identify determinant variables. Findings were presented in texts and tables.
METHODS: The medical charts of participants were reviewed to identify those who had developed puerperal sepsis.
RESULTS: Anaemia (AOR 6.05; 95% CI 2.57 to 14.26), undernourishment (AOR 4.43; 95% CI 1.96 to 10.01), gestational diabetes mellitus (AOR 3.26; 95% CI 1.22 to 8.74), postpartum haemorrhage (AOR 3.17; 95% CI 1.28 to 7.87), obstructed labour (AOR 2.76; 95% CI 1.17 to 6.52), multiparity (AOR 2.54; 95% CI 1.17 to 5.50), placenta previa (AOR 2.27; 95% CI 1.11 to 4.67) and vaginal examination ≥5 times (AOR 2.19; 95% CI 1.05 to 4.54) were the independent determinants of puerperal sepsis in this study.
CONCLUSIONS: This study found that gestational diabetes mellitus, anaemia, undernourishment, placenta previa, obstructed labour, postpartum haemorrhage and five or more per-vaginal examinations during labour were the determinants of puerperal sepsis. Therefore, it is recommended that obstetric care providers strictly adhere to guidelines on the number of vaginal exams that should be performed throughout labour and that they perform these exams using the appropriate infection-prevention techniques. In addition, they should provide comprehensive health education on nutrition during pregnancy and postnatal periods and the importance of iron supplements.

Sepsis is a widespread and life-threatening disease characterised by infection-triggered immune hyperactivation and cytokine storms, culminating in tissue damage and multiple organ dysfunction syndrome. BMAL1 is a pivotal transcription factor in the circadian clock that plays a crucial role in maintaining immune homeostasis. BMAL1 dysregulation has been implicated in inflammatory diseases and immunodeficiency. However, the mechanisms underlying BMAL1 disruption in sepsis-induced acute lung injury (ALI) remain poorly understood. In vitro, we used THP1 and mouse peritoneal macrophages to elucidate the potential mechanism of BMAL1 function in sepsis. In vivo, an endotoxemia model was used to investigate the effect of BMAL1 on sepsis and the therapeutic role of targeting CXCR2. We showed that BMAL1 significantly affected the regulation of innate immunity in sepsis-induced ALI. BMAL1 deficiency in the macrophages exacerbated systemic inflammation and sepsis-induced ALI. Mechanistically, BMAL1 acted as a transcriptional suppressor and regulated the expression of CXCL2. BMAL1 deficiency in macrophages upregulated CXCL2 expression, increasing the recruitment of polymorphonuclear neutrophils and the formation of neutrophil extracellular traps (NETs) by binding to the chemokine receptor CXCR2, thereby intensifying lung injury in a sepsis model. Furthermore, a selective inhibitor of CXCR2, SB225002, exerted promising therapeutic effects by markedly reducing neutrophil infiltration and NETs formation and alleviating lung injury. Importantly, CXCR2 blockade mitigated multiple organ dysfunction. Collectively, these findings suggest that BMAL1 controls the CXCL2/CXCR2 pathway, and the therapeutic efficacy of targeting CXCR2 in sepsis has been validated, presenting BMAL1 as a potential therapeutic target for lethal infections.