Resolvin D2 attenuates LPS-induced macrophage exhaustion.

Early in sepsis, a hyperinflammatory response is dominant, but later, an immunosuppressive phase dominates, and the host is susceptible to opportunistic infections. Anti-inflammatory agents may accelerate the host into immunosuppression, and few agents can reverse immunosuppression without causing inflammation. Specialized pro-resolving mediators (SPMs) such as resolvin D2 (RvD2) have been reported to resolve inflammation without being immunosuppressive, but little work has been conducted to examine their effects on immunosuppression. To assess the effects of RvD2 on immunosuppression, we established a model of macrophage exhaustion using two lipopolysaccharide (LPS) treatments or hits. THP-1 monocyte-derived macrophages were first treated with RvD2 or vehicle for 1 h. One LPS hit increased NF-κB activity 11-fold and TNF-α release 60-fold compared to unstimulated macrophages. RvD2 decreased LPS-induced NF-κB activity and TNF-α production but increased bacterial clearance. Two LPS hits reduced macrophage bacterial clearance and decreased macrophage NF-κB activity (45%) and TNF-α release (75%) compared to one LPS hit, demonstrating exhaustion. RvD2 increased NF-κB activity, TNF-α release, and bacterial clearance following two LPS hits compared to controls. TLR2 inhibition abolished RvD2-mediated changes. In a mouse sepsis model, splenic macrophage response to exogenous LPS was reduced compared to controls and was restored by in vivo administration of RvD2, supporting the in vitro results. If RvD2 was added to monocytes before differentiation into macrophages, however, RvD2 reduced LPS responses and increased bacterial clearance following both one and two LPS hits. The results show that RvD2 attenuated macrophage suppression in vitro and in vivo and that this effect was macrophage-specific.

A new approach to describe the taxonomic structure of microbiome and its application to assess the relationship between microbial niches.

BACKGROUND: Data from microbiomes from multiple niches is often collected, but methods to analyse these often ignore associations between niches. One interesting case is that of the oral microbiome. Its composition is receiving increasing attention due to reports on its associations with general health. While the oral cavity includes different niches, multi-niche microbiome data analysis is conducted using a single niche at a time and, therefore, ignores other niches that could act as confounding variables. Understanding the interaction between niches would assist interpretation of the results, and help improve our understanding of multi-niche microbiomes. METHODS: In this study, we used a machine learning technique called latent Dirichlet allocation (LDA) on two microbiome datasets consisting of several niches. LDA was used on both individual niches and all niches simultaneously. On individual niches, LDA was used to decompose each niche into bacterial sub-communities unveiling their taxonomic structure. These sub-communities were then used to assess the relationship between microbial niches using the global test. On all niches simultaneously, LDA allowed us to extract meaningful microbial patterns. Sets of co-occurring operational taxonomic units (OTUs) comprising those patterns were then used to predict the original location of each sample. RESULTS: Our approach showed that the per-niche sub-communities displayed a strong association between supragingival plaque and saliva, as well as between the anterior and posterior tongue. In addition, the LDA-derived microbial signatures were able to predict the original sample niche illustrating the meaningfulness of our sub-communities. For the multi-niche oral microbiome dataset we had an overall accuracy of 76%, and per-niche sensitivity of up to 83%. Finally, for a second multi-niche microbiome dataset from the entire body, microbial niches from the oral cavity displayed stronger associations to each other than with those from other parts of the body, such as niches within the vagina and the skin. CONCLUSION: Our LDA-based approach produces sets of co-occurring taxa that can describe niche composition. LDA-derived microbial signatures can also be instrumental in summarizing microbiome data, for both descriptions as well as prediction.

KIDS SAVE LIVES: Basic Life Support Education for Schoolchildren: A Narrative Review and Scientific Statement From the International Liaison Committee on Resuscitation.

BACKGROUND: Basic life support education for schoolchildren has become a key initiative to increase bystander cardiopulmonary resuscitation rates. Our objective was to review the existing literature on teaching schoolchildren basic life support to identify the best practices to provide basic life support training in schoolchildren. METHODS: After topics and subgroups were defined, a comprehensive literature search was conducted. Systematic reviews and controlled and uncontrolled prospective and retrospective studies containing data on students <20 years of age were included. RESULTS: Schoolchildren are highly motivated to learn basic life support. The CHECK-CALL-COMPRESS algorithm is recommended for all schoolchildren. Regular training in basic life support regardless of age consolidates long-term skills. Young children from 4 years of age are able to assess the first links in the chain of survival. By 10 to 12 years of age, effective chest compression depths and ventilation volumes can be achieved on training manikins. A combination of theoretical and practical training is recommended. Schoolteachers serve as effective basic life support instructors. Schoolchildren also serve as multipliers by passing on basic life support skills to others. The use of age-appropriate social media tools for teaching is a promising approach for schoolchildren of all ages. CONCLUSIONS: Schoolchildren basic life support training has the potential to educate whole generations to respond to cardiac arrest and to increase survival after out-of-hospital cardiac arrest. Comprehensive legislation, curricula, and scientific assessment are crucial to further develop the education of schoolchildren in basic life support.

2023 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations: Summary From the Basic Life Support; Advanced Life Support; Pediatric Life Support; Neonatal Life Support; Education, Implementation, and Teams; and First Aid Task Forces.

The International Liaison Committee on Resuscitation engages in a continuous review of new, peer-reviewed, published cardiopulmonary resuscitation and first aid science. Draft Consensus on Science With Treatment Recommendations are posted online throughout the year, and this annual summary provides more concise versions of the final Consensus on Science With Treatment Recommendations from all task forces for the year. Topics addressed by systematic reviews this year include resuscitation of cardiac arrest from drowning, extracorporeal cardiopulmonary resuscitation for adults and children, calcium during cardiac arrest, double sequential defibrillation, neuroprognostication after cardiac arrest for adults and children, maintaining normal temperature after preterm birth, heart rate monitoring methods for diagnostics in neonates, detection of exhaled carbon dioxide in neonates, family presence during resuscitation of adults, and a stepwise approach to resuscitation skills training. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the quality of the evidence, using Grading of Recommendations Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence-to-Decision Framework Highlights sections. In addition, the task forces list priority knowledge gaps for further research. Additional topics are addressed with scoping reviews and evidence updates.

Resolvin T-series reduce neutrophil extracellular traps.

The newly identified 13-series (T-series) resolvins (RvTs) regulate phagocyte functions and accelerate resolution of infectious inflammation. Because severe acute respiratory syndrome coronavirus 2 elicits uncontrolled inflammation involving neutrophil extracellular traps (NETs), we tested whether stereochemically defined RvTs regulate NET formation. Using microfluidic devices capturing NETs in phorbol 12-myristate 13-acetate-stimulated human whole blood, the RvTs (RvT1-RvT4; 2.5 nM each) potently reduced NETs. With interleukin-1ß-stimulated human neutrophils, each RvT dose and time dependently decreased NETosis, conveying ∼50% potencies at 10 nM, compared with a known NETosis inhibitor (10 µM). In a murine Staphylococcus aureus infection, RvTs (50 ng each) limited neutrophil infiltration, bacterial titers, and NETs. In addition, each RvT enhanced NET uptake by human macrophages; RvT2 was the most potent of the four RvTs, giving a >50% increase in NET-phagocytosis. As part of the intracellular signaling mechanism, RvT2 increased cyclic adenosine monophosphate and phospho-AMP-activated protein kinase (AMPK) within human macrophages, and RvT2-stimulated NET uptake was abolished by protein kinase A and AMPK inhibition. RvT2 also stimulated NET clearance by mouse macrophages in vivo. Together, these results provide evidence for novel pro-resolving functions of RvTs, namely reducing NETosis and enhancing macrophage NET clearance via a cyclic adenosine monophosphate-protein kinase A-AMPK axis. Thus, RvTs open opportunities for regulating NET-mediated collateral tissue damage during infection as well as monitoring NETs.

Lipoxin A4 promotes antibiotic and monocyte bacterial killing in established Pseudomonas aeruginosa biofilm formed under hydrodynamic conditions.

Pseudomonas aeruginosa is a gram-negative, opportunistic bacteria commonly found in wounds and in lungs of immunocompromised patients. These bacteria commonly form biofilms which encapsulate the bacteria, making it difficult for antibiotics or immune cells to reach the bacterial cells. We previously reported that Lipoxin A4 (LxA4 ), a Specialized Pro-resolving Mediator, has direct effects on P. aeruginosa where it reduced biofilm formation and promoted ciprofloxacin antibiotic efficacy in a static biofilm-forming system. In the current studies, we examined the actions of LxA4 on established biofilms formed in a biofilm reactor under dynamic conditions with constant flow and shear stress. These conditions allow for biofilm growth with nutrient replenishment and for examination of bacteria within the biofilm structure. We show that LxA4 helped ciprofloxacin reduction of live/dead ratio of bacteria within the biofilm. THP-1 monocytes interacted with the biofilm to increase the number of viable bacteria within the biofilm as well as TNF-α production in the biofilm milieu, suggesting that monocyte interaction with bacterial biofilm exacerbates the inflammatory state. Pre-treatment of the THP-1 monocytes with LxA4 abolished the increase in biofilm bacteria and reduced TNF-α production. The effect of decreased biofilm bacteria was associated with increased LxA4 -induced monocyte adherence to biofilm but not increased bacteria killing suggesting that the mechanism for the reduced biofilm bacteria was due to LxA4 -mediated increase in adherence to biofilm. These results suggest that LxA4 can help antibiotic efficacy and promote monocyte activity against established P. aeruginosa biofilm formed under hydrodynamic conditions.

Effectiveness of antibacterial therapeutic clothing vs. nonantibacterial therapeutic clothing in patients with moderate-to-severe atopic dermatitis: a randomized controlled observer-blind pragmatic trial (ABC trial).

BACKGROUND: Increased Staphylococcus aureus (SA) colonization is considered an important factor in the pathogenesis of atopic dermatitis (AD). Antibacterial therapeutic clothing aims to reduce SA colonization and AD inflammation; however, its role in the management of AD remains poorly understood. OBJECTIVES: To investigate the effectiveness of antibacterial therapeutic clothing + standard topical treatment in patients with moderate-to-severe AD vs. standard therapeutic clothing + standard topical treatment; and, if effectiveness was demonstrated, to demonstrate its cost-effectiveness. METHODS: A pragmatic double-blinded multicentre randomized controlled trial (NCT04297215) was conducted in patients of all ages with moderate-to-severe AD. Patients were centrally randomized 1 : 1 : 1 to receive standard therapeutic clothing or antibacterial clothing based on chitosan or silver. The primary outcome was the between-group difference in Eczema Area and Severity Index (EASI) measured over 52 weeks. Secondary outcomes included patient-reported outcomes (PROs), topical corticosteroid (TCS) use, SA colonization, safety and cost-effectiveness. Outcomes were assessed by means of (generalized) linear mixed-model analyses. RESULTS: Between 16 March 2020 and 20 December 2021, 171 patients were enrolled. In total, 159 patients were included (54 in the standard therapeutic clothing group, 50 in the chitosan group and 55 in the silver group). Adherence was high [median 7 nights a week wear (interquartile range 3-7)]. Median EASI scores at baseline and at 4, 12, 26 and 52 weeks were 11.8, 4.3, 4.6, 4.2 and 3.6, respectively, in the standard therapeutic clothing group vs. 11.3, 5.0, 3.0, 3.0 and 4.4, respectively, in the chitosan group, and 11.6, 5.0, 5.4, 4.6 and 5.8, respectively, in the silver group. No differences in EASI over 52 weeks between the standard therapeutic clothing group, the chitosan group [-0.1, 95% confidence interval (CI) -0.3 to 0.2; P = 0.53] or the silver group (-0.1, 95% CI -0.3 to 0.2; P = 0.58) were found. However, a small significant group × time interaction effect between the standard and silver groups was found (P = 0.03), in which the silver group performed worse after 26 weeks. No differences between groups were found in PROs, TCS use, SA skin colonization and healthcare utilization. No severe adverse events or silver absorption were observed. CONCLUSIONS: The results of this study suggest no additional benefits of antibacterial agents in therapeutic clothing in patients with moderate-to-severe AD.

Comparing binary efficacy outcomes for systemic immunomodulatory treatments for atopic dermatitis in a living systematic review and network meta-analysis.

BACKGROUND: Systemic treatments for atopic dermatitis (AD) are evaluated primarily in placebo-controlled trials with binary efficacy outcomes. In a living systematic review and network meta-analysis (NMA), we previously analysed continuous efficacy measures. OBJECTIVES: To compare binary efficacy outcomes of systemic treatments for AD. METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Latin American and Caribbean Health Science Information (LILACS) database, Global Resource for Eczema Trials (GREAT) database and trial registries up to 1 March 2023. We included randomized trials examining ≥ 8 weeks of treatment with systemic immunomodulatory medications for moderate-to-severe AD. We screened titles, abstracts and full texts and abstracted data independently, in duplicate. Outcomes included the proportion of patients achieving at least 50%, 75% and 90% improvements in Eczema Area and Severity Index (EASI 50, EASI 75 and EASI 90, respectively) and Investigator Global Assessment (IGA) success. We performed random-effects Bayesian NMAs to calculate odds ratios (OR) and 95% credible intervals (CrIs) between each intervention for each outcome. RESULTS: Eighty-three trials with 22 122 participants were included in the systematic review. In analyses limited to trials of 8-16 weeks' duration with predominantly adult populations, abrocitinib 200 mg daily (OR 1.5, 95% CrI 1.1-2.2) and upadacitinib 15 mg daily (OR 1.7, 95% CrI 0.9-3.3) and 30 mg daily (OR 2.5, 95% CrI 1.3-5.0) were associated with higher odds of achieving EASI 50 vs. dupilumab. Abrocitinib 100 mg daily (OR 0.7, 95% CrI 0.5-1.0), baricitinib 2 mg daily (OR 0.4, 95% CrI 0.3-0.5) and 4 mg daily (OR 0.5, 95% CrI 0.3-0.7), and tralokinumab (OR 0.4, 95% CrI 0.3-0.6) were associated with lower odds of achieving EASI 50 vs. dupilumab. Results were similar for EASI 75, EASI 90 and IGA success. CONCLUSIONS: Supporting results for continuous outcome measures, upadacitinib 30 mg daily and abrocitinib 200 mg daily are the most efficacious with regard to binary efficacy endpoints up to 16 weeks in adults with moderate-to-severe AD, followed by upadacitinib 15 mg daily, dupilumab and abrocitinib 100 mg daily. Dupilumab and both doses of upadacitinib and abrocitinib are more efficacious than baricitinib 4 and 2 mg daily and tralokinumab.

Defining disease severity in atopic dermatitis and psoriasis for the application to biomarker research: an interdisciplinary perspective.

More severe atopic dermatitis and psoriasis are associated with a higher cumulative impact on quality of life, multimorbidity and healthcare costs. Proactive, early intervention in those most at risk of severe disease may reduce this cumulative burden and modify the disease trajectory to limit progression. The lack of reliable biomarkers for this at-risk group represents a barrier to such a paradigm shift in practice. To expedite discovery and validation, the BIOMarkers in Atopic Dermatitis and Psoriasis (BIOMAP) consortium (a large-scale European, interdisciplinary research initiative) has curated clinical and molecular data across diverse study designs and sources including cross-sectional and cohort studies (small-scale studies through to large multicentre registries), clinical trials, electronic health records and large-scale population-based biobanks. We map all dataset disease severity instruments and measures to three key domains (symptoms, inflammatory activity and disease course), and describe important codependencies and relationships across variables and domains. We prioritize definitions for more severe disease with reference to international consensus, reference standards and/or expert opinion. Key factors to consider when analysing datasets across these diverse study types include explicit early consideration of biomarker purpose and clinical context, candidate biomarkers associated with disease severity at a particular point in time and over time and how they are related, taking the stage of biomarker development into account when selecting disease severity measures for analyses, and validating biomarker associations with disease severity outcomes using both physician- and patient-reported measures and across domains. The outputs from this exercise will ensure coherence and focus across the BIOMAP consortium so that mechanistic insights and biomarkers are clinically relevant, patient-centric and more generalizable to current and future research efforts.

Atopic dermatitis (AD), and psoriasis are long-term skin conditions that can significantly affect people's lives, especially when symptoms are severe. Approximately 10% of adults and 20% of children are affected by AD, while psoriasis affects around 5% of people in the UK. Both conditions are associated with debilitating physical symptoms (such as itch) and have been linked to depression and anxiety. Biomarkers are naturally occurring chemicals in the human body and have potential to enhance the longer-term management of AD and psoriasis. Currently, there are no routinely used biomarkers that can identify people who experience or will go on to develop severe AD and psoriasis. For this reason, research is under way to understand which biomarkers are linked to severity. In this study, a multidisciplinary team of skin researchers from across Europe, along with patient groups, discussed the complexities of studying severity-related biomarkers. We identified a number of severity measurement approaches and there were recommendations for future biomarker research, including (i) considering multiple measures as no single measure can encompass all aspects of severity, (ii) exploring severity measures recorded by both healthcare professionals and patients, as each may capture different aspects, and (iii) accounting for influencing factors, such as different treatment approaches, that may impact AD and psoriasis severity, which make it challenging to compare findings across studies. Overall, we anticipate that the insights gained from these discussions will increase the likelihood of biomarkers being effectively applied in real-world settings, to ultimately improve outcomes for people with AD and psoriasis.

Comparing Simulation Training of Bronchoscopy-Guided Percutaneous Dilatational Tracheostomy Using Conventional Versus 3D Printed Simulators (TRAC-Sim Study).

Background: Individual implementation rate of bronchoscopy-guided percutaneous dilatational tracheostomy (PDT) varies among intensivists. Simulation training (ST) can increase the safety of medical procedures by reducing stress levels of the performing team. The aim of this study was to evaluate the benefit of ST in PDT regarding procedural time, quality of performance, and percepted feelings of safety of the proceduralist and to compare conventional simulators (CSIM) with simulators generated from 3D printers (3DSIM). Methods: We conducted a prospective, single-center, randomized, blinded cross-over study comparing the benefit of CSIM versus 3DSIM for ST of PDT. Participants underwent a standardized theoretical training and were randomized to ST with CSIM (group A) or 3DSIM (group B). After ST, participants' performance was assessed by two blinded examiners on a porcine trachea regarding time required for successful completion of PDT and correct performance (assessed by a performance score). Percepted feelings of safety were assessed before and after ST. This was followed by a second training and second assessment of the same aspects with crossed groups. Results: 44 participants were included: 24 initially trained with CSIM (group A) and 20 with 3DSIM (group B). Correctness of the PDT performance increased significantly in group B (p < .01) and not significantly in group A (p = .14). Mean procedural time required for performing a PDT after their second ST compared to the first assessment (p < .01) was lower with no difference between group A and group B and irrespective of the participants' previous experience regarding PDT, age, and sex. Moreover, percepted feelings of safety increased after the first ST in both groups (p < .001). Conclusions: ST can improve procedural skills, procedural time, and percepted feelings of safety of the proceduralist in simulated PDT.

Is Telemedicine Suitable for Patients with Chronic Inflammatory Skin Conditions? A Systematic Review.

Telemedicine, the provision of remote healthcare, has gained prominence, accelerated by the COVID-19 pandemic. It has the potential to replace routine in-person follow-up visits for patients with chronic inflammatory skin conditions. However, it remains unclear whether telemedicine can effectively substitute in-person consultations for this patient group. This systematic review assessed the effectiveness and safety of telemedicine compared with traditional in-person care for chronic inflammatory skin diseases. A comprehensive search in various databases identified 11 articles, including 5 randomized controlled trials (RCTs) and 1 clinical controlled trial (CCT). These studies evaluated telemedicine's impact on patients with psoriasis and atopic dermatitis, with varying methods like video consultations and digital platforms. The findings tentatively suggest that telemedicine does not seem to be inferior compared with in-person care, particularly in terms of condition severity and quality of life for patients with chronic inflammatory skin diseases. However, these results should be interpreted with caution due to the inherent uncertainties in the evidence. There are indications that telemedicine can offer benefits such as cost-effectiveness, time savings, and reduced travel distances, but it is important to recognize these findings as preliminary, necessitating further validation through more extensive research.

Weaning failure due to isolated residual diaphragmatic paralysis after cervical spinal cord ischemia following aortic surgery- a case report.

BACKGROUND: Bilateral diaphragmatic dysfunction can lead to dyspnea and recurrent respiratory failure. In rare cases, it may result from high cervical spinal cord ischemia (SCI) due to anterior spinal artery syndrome (ASAS). We present a case of a patient experiencing persistent isolated diaphragmatic paralysis after SCI at level C3/C4 following thoracic endovascular aortic repair (TEVAR) for Kommerell's diverticulum. This is, to our knowledge, the first documented instance of a patient fully recovering from tetraplegia due to SCI while still exhibiting ongoing bilateral diaphragmatic paralysis. CASE PRESENTATION: The patient, a 67-year-old male, presented to the Vascular Surgery Department for surgical treatment of symptomatic Kommerell's diverticulum in an aberrant right subclavian artery. After successful surgery in two stages, the patient presented with respiratory insufficiency and flaccid tetraparesis consistent with anterior spinal artery syndrome with maintained sensibility of all extremities. A computerized tomography scan (CT) revealed a high-grade origin stenosis of the left vertebral artery, which was treated by angioplasty and balloon-expandable stenting. Consecutively, the tetraparesis immediately resolved, but weaning remained unsuccessful requiring tracheostomy. Abdominal ultrasound revealed a residual bilateral diaphragmatic paralysis. A repeated magnetic resonance imaging (MRI) 14 days after vertebral artery angioplasty confirmed SCI at level C3/C4. The patient was transferred to a pulmonary clinic with weaning center for further recovery. CONCLUSIONS: This novel case highlights the need to consider diaphragmatic paralysis due to SCI as a cause of respiratory failure in patients following aortic surgery. Diaphragmatic paralysis may remain as an isolated residual in these patients.

Intraoperative Assessment of Noninvasive Left Ventricular Myocardial Work Indices in Patients Undergoing Aortic Valve Replacement.

OBJECTIVE: Evaluation of noninvasive left ventricular (LV) myocardial work (MW) enables insights into cardiac contractility and efficacy beyond conventional echocardiography. However, there is limited intraoperative data on patients undergoing surgical aortic valve replacement (AVR). The aim of this study was to describe the feasibility and the intraoperative course of this technique of ventricular function assessment in these patients and compare it to conventional two (2D)- and three-dimensional (3D) echocardiographic measurements and strain analysis. DESIGN: Prospective observational study. SETTING: Single university hospital. PARTICIPANTS: Twenty-five patients scheduled for isolated AVR with preoperative preserved left and right ventricular function, sinus rhythm, without significant other heart valve disease or pulmonary hypertension, and an uneventful intraoperative course. INTERVENTIONS: Transesophageal echocardiography was performed after induction of anesthesia (T1), after termination of cardiopulmonary bypass (T2), and after sternal closure (T3). Evaluation was performed in stable hemodynamics, in sinus rhythm or atrial pacing and vasopressor support with norepinephrine ≤ 0.1 µg/kg/min. MEASUREMENTS AND MAIN RESULTS: EchoPAC v206 software (GE Vingmed Ultrasound AS, Norway) was used for analysis of 2D and 3D LV ejection fraction (EF), LV global longitudinal strain (GLS), LV global work index (GWI), LV global constructive work (GCW), LV global wasted work (GWW), and LV global work efficiency (GWE). Estimation of myocardial work was feasible in all patients. Although there was no significant difference in the values of 2D and 3D EF, GWI and GCW decreased significantly after AVR (T1 v T2, 1,647 ± 380 mmHg% v 1,021 ± 233 mmHg%, p < 0.001; T1 v T2, 2,095 ± 433 mmHg% v 1,402 ± 242 mmHg%, p < 0.001, respectively), while GWW remained unchanged (T1 v T2, 296 mmHg% [IQR 178-452) v 309 mmHg% [IQR 255-438), p = 0.97). This resulted in a decreased GWE directly after bypass (T1 v T2, 84% ± 6% v 78% ± 5%, p < 0.001), but GWE already improved at the end of surgery (T2 v T3, 78% ± 5% v 81% ± 5%, p = 0.003). There was no significant change in the values of GWI, GCW, or 2D and 3D LVEF before and after sternal closure (T2 v T3). CONCLUSION: LV MW analysis showed a reduction of LV workload after bypass in our group of patients, which was not detected by conventional echocardiographic measures. This evolving technique provides deeper insights into cardiac energetics and efficiency in the perioperative course of aortic valve replacement surgery.

Evaluation of Intraoperative Left-Ventricular Diastolic Function by Myocardial Strain in On-Pump Coronary Artery Bypass Surgery.

OBJECTIVES: Left ventricular (LV) diastolic function strongly predicts outcomes after cardiac surgery, but there is no consensus about appropriate intraoperative assessment. Recently, intraoperative diastolic strain-based measurements assessed by transesophageal echocardiography (TEE) have shown a strong correlation with LV relaxation, compliance, and filling, but there are no reports about evaluation through the entire perioperative period. Therefore, the authors describe the intraoperative course of this novel assessment technique in patients who underwent coronary artery bypass grafting, and compare it with conventional echocardiographic measures and common grading algorithms of LV diastolic dysfunction (LVDD). DESIGN: Prospectively obtained data. SETTING: A single university hospital. PARTICIPANTS: Thirty adult patients scheduled for isolated on-pump coronary artery bypass grafting surgery with preoperative preserved left and right ventricular systolic function, without significant heart valve disease and pulmonary hypertension, and an uneventful intraoperative course were included. INTERVENTIONS: Transesophageal echocardiography was performed after induction of anesthesia (T1), after termination of cardiopulmonary bypass (T2), and after sternal closure (T3). Echocardiographic evaluation was performed in stable hemodynamic conditions, in sinus rhythm or atrial pacing, and vasopressor support with norepinephrine ≤0.1 µg/kg/min. MEASUREMENTS AND MAIN RESULTS: Strain-based measurements of peak longitudinal strain rate during isovolumetric relaxation (SR-IVR) and during early (SR-E) and late (SR-A) LV filling were assessed using EchoPAC v204 software (GE Vingmed Ultrasound AS, Norway). Evaluation of conventional echocardiographic parameters included transmitral Doppler measures of early (E) and late (A) LV filling, as well as lateral-tissue Doppler velocity assessed during early (e´) and late (a´) LV filling, tricuspid regurgitation, and left atrial dilatation. Evaluation and grading of LV diastolic function by myocardial strain was feasible in all included patients at all time points of assessment. Using conventional grading algorithms, however, a substantial number of patients could not be sufficiently graded, falling into an indeterminate zone and not reliably estimating LVDD (T1, 40%; T2, 33%; T3, 36%). There was significant impairment of LV diastolic function after bypass, as measured by SR-IVR (T1 v T2, 0.28 s-1 [IQR 0.23; 0.31) v 0.18 s-1 [IQR 0.14; 0.22]; p < 0.001), SR-E (T1 v T2, 0.95 ± 0.34 s-1v 1.28 ± 0.36 s-1; p < 0.001), and E/SR-IVR (T1 v T2, 2.3 ± 1.0 m v 4.5 ± 2.1 m; p < 0.001]. Conventional echocardiographic measures remained unchanged during the same period (E/A T1 v T2, 1.27 [IQR 0.94; 1.59] v 1.21 [IQR 1.03; 1.47] [p = 1] and E/e´ T1 v T2, 7.0 [IQR 5.3; 9.6] v 6.35 [IQR 5.7; 9.9] [p = 0.9]). There were no significant changes in the values of SR-IVR, SR-E, SR-A, E/SR-IVR, E/A, and E/e´ before and after sternal closure (T2 v T3). CONCLUSION: Intraoperative assessment of strain-based measurements of LV diastolic function and strain-based LVDD grading was feasible in this group of selected patients, whereas conventional parameters failed to describe LVDD sufficiently in a substantial number of patients. Diastolic strain-based measurements showed impairment of LV relaxation and compliance after bypass, which was not detected by conventional echocardiographic parameters. Therefore, diastolic myocardial strain analysis might be more sensitive in detecting myocardial diastolic dysfunction by TEE in the perioperative setting, with its dynamic changes of loading conditions, and might provide valuable and additional information on the perioperative changes of LV diastolic function.

Global Guidelines in Dermatology Mapping Project (GUIDEMAP)-A systematic review of the methodological quality of contact dermatitis clinical practice guidelines.

The Global Guidelines in Dermatology Mapping Project (GUIDEMAP) assesses the methodological quality of clinical practice guidelines (CPGs) for high-burden skin diseases. This review focuses on contact dermatitis. We searched MEDLINE, Embase, PubMed, Web of Science, Cochrane Library, Emcare, Epistemonikos, PsycINFO and Academic Search Premier for CPGs published between 1 November 2018 and 1 November 2023. Prespecified guideline resources were hand searched. Two authors independently undertook screening, data extraction and quality assessments. Instruments used were the Appraisal of Guidelines for Research and Evaluation (AGREE) II Reporting Checklist, the U.S. Institute of Medicine's (IOM) criteria of trustworthiness, The Agency for Healthcare Research and Quality's National Guideline Clearinghouse Extent Adherence to Trustworthy Standards (NEATS) Instrument and Lenzer's Red Flags. Twenty five CPGs were included, exhibiting heterogeneity in both the topics they addressed and their methodological quality. Whereas the CPGs on management of hand eczema from Denmark, Europe and the Netherlands scored best, most CPGs fell short of being clear, unbiased, trustworthy and evidence-based. Disclosure of conflicts of interest scored well, and areas needing improvement include 'strength and wording of recommendations', 'applicability', 'updating' and 'external review'. Adhering to AGREE II and Grading of Recommendations, Assessment, Development and Evaluations (GRADE) enhances methodological quality.

Postoperative Pain Following Eye Enucleation: A Prospective Observational Study.

Background and Objectives: Enucleation of an eye is the most invasive procedure in ophthalmologic surgery. It can be the result of various diseases (malignant/chronic/trauma/infection) and is nevertheless relatively rare, but leads to the loss of a strongly innervated neuronal organ. This study systematically evaluates postoperative pain levels following enucleation of the eye globe. Materials and Methods: This prospective single-center study enrolled twenty-four patients undergoing enucleation of the eye globe. Perioperatively all patients completed (preoperative day, day of surgery, 1st, 2nd, and 3rd day following surgery) standardized questionnaires concerning their pain experience and treatment-related side-effects (internal protocol, QUIPS, painDETECT®). Patients received usual pain therapy in an unstandardized individual manner. Results: Preoperatively, mean average pain intensity of all included patients was 3.29 ± 2.46 (range, 0-8), 3.29 ± 3.24 (range, 0-8) on the day of surgery, 4.67 ± 1.90 (range, 2-10) on day 1, 3.25 ± 1.39 (range, 1-6) on day 2, and 2.71 ± 1.30 (range, 1-6) on day 3 after surgery. Mean maximum pain intensity was 4.71 ± 3.28 (range, 0-10) preoperatively, 4.04 ± 3.78 (range, 0-10) on the day of surgery, 5.75 ± 2.01 (range, 2-10) on day 1, 4.25 ± 1.89 (range, 2-10) on day 2, and 3.88 ± 1.54 (range, 2-8) on day 3 after surgery. Nineteen patients (79.2%) stated that they would have preferred more pain therapy. Conclusions: Patients undergoing eye enucleation report pain sensations in need of intervention in this university hospital. Thus, effective standardized pain treatment concepts are now a high priority to be established in an interdisciplinary manner containing standardized regimens and continuous regional procedures. Awareness of this problem in the medical team should be sharpened through targeted training and information.

2022 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations: Summary From the Basic Life Support; Advanced Life Support; Pediatric Life Support; Neonatal Life Support; Education, Implementation, and Teams; and First Aid Task Forces.

This is the sixth annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. This summary addresses the most recently published resuscitation evidence reviewed by International Liaison Committee on Resuscitation Task Force science experts. Topics covered by systematic reviews include cardiopulmonary resuscitation during transport; approach to resuscitation after drowning; passive ventilation; minimizing pauses during cardiopulmonary resuscitation; temperature management after cardiac arrest; use of diagnostic point-of-care ultrasound during cardiac arrest; use of vasopressin and corticosteroids during cardiac arrest; coronary angiography after cardiac arrest; public-access defibrillation devices for children; pediatric early warning systems; maintaining normal temperature immediately after birth; suctioning of amniotic fluid at birth; tactile stimulation for resuscitation immediately after birth; use of continuous positive airway pressure for respiratory distress at term birth; respiratory and heart rate monitoring in the delivery room; supraglottic airway use in neonates; prearrest prediction of in-hospital cardiac arrest mortality; basic life support training for likely rescuers of high-risk populations; effect of resuscitation team training; blended learning for life support training; training and recertification for resuscitation instructors; and recovery position for maintenance of breathing and prevention of cardiac arrest. Members from 6 task forces have assessed, discussed, and debated the quality of the evidence using Grading of Recommendations Assessment, Development, and Evaluation criteria and generated consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence-to-Decision Framework Highlights sections, and priority knowledge gaps for future research are listed.

2021 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations: Summary From the Basic Life Support; Advanced Life Support; Neonatal Life Support; Education, Implementation, and Teams; First Aid Task Forces; and the COVID-19 Working Group.

The International Liaison Committee on Resuscitation initiated a continuous review of new, peer-reviewed published cardiopulmonary resuscitation science. This is the fifth annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations; a more comprehensive review was done in 2020. This latest summary addresses the most recently published resuscitation evidence reviewed by International Liaison Committee on Resuscitation task force science experts. Topics covered by systematic reviews in this summary include resuscitation topics of video-based dispatch systems; head-up cardiopulmonary resuscitation; early coronary angiography after return of spontaneous circulation; cardiopulmonary resuscitation in the prone patient; cord management at birth for preterm and term infants; devices for administering positive-pressure ventilation at birth; family presence during neonatal resuscitation; self-directed, digitally based basic life support education and training in adults and children; coronavirus disease 2019 infection risk to rescuers from patients in cardiac arrest; and first aid topics, including cooling with water for thermal burns, oral rehydration for exertional dehydration, pediatric tourniquet use, and methods of tick removal. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the quality of the evidence, according to the Grading of Recommendations Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations or good practice statements. Insights into the deliberations of the task forces are provided in Justification and Evidence-to-Decision Framework Highlights sections. In addition, the task forces listed priority knowledge gaps for further research.

Stereochemistry and functions of the new cysteinyl-resolvin, 4S,5R-RCTR1, in efferocytosis and erythrophagocytosis of human senescent erythrocytes.

Specialized pro-resolving lipid mediators play key functions in the resolution of the acute inflammatory response. Herein, we elucidate the stereochemical structure of the new 4S,5R-RCTR1, a cysteinyl-resolvin, recently uncovered in human leukocytes incubated with a 4S,5S-epoxy-resolvin intermediate, using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and ultra-violet (UV) spectrophotometry. With this approach, the physical properties of the new mediator prepared by total organic synthesis were matched to enzymatically produced biogenic material. In addition, we confirmed the potent biological actions of 4S,5R-RCTR1 with human M2-like macrophage phagocytosis of live bacteria, efferocytosis of apoptotic neutrophils, and erythrophagocytosis of senescent human red blood cells in a concentration-dependent manner from 0.1 to 10 nM. Taken together, these results establish the complete stereochemistry of 4S,5R-RCTR1 as 5R-glutathionyl-4S,17S-dihydroxy-6E,8E,10Z,13Z,15E,19Z-docosahexaenoic acid and give evidence of its novel bioactivities in human phagocyte responses. Moreover, they confirm and extend the stereoselective functions of the 4S,5R-RCTR1 with isolated human phagocytes of interest in the resolution of inflammation.

Telephone cardiopulmonary resuscitation, first responder systems, cardiac arrest centers, and global campaigns to save lives.

PURPOSE OF REVIEW: The latest resuscitation guidelines contain a new chapter, which focuses on systems improving care for patients with out-of-hospital cardiac arrest (OHCA). In this article, we describe recent developments regarding telephone cardiopulmonary resuscitation (CPR), first responder systems, cardiac arrest centers, and global campaigns. RECENT FINDINGS: Telephone CPR has been implemented in many countries, and recent developments include artificial intelligence and video calls to improve dispatch assisted CPR. However, the degree of implementation is not yet satisfying. Smartphone alerting systems are effective in reducing the resuscitation-free interval, but many regions do not yet use this technology. Further improvements are needed to reduce response times. Cardiac arrest centers increase the survival chance after OHCA. Specific criteria need to be defined and professional societies should establish a certification process. Global campaigns are effective in reaching people around the world. However, we need to evaluate the effects of the campaigns. SUMMARY: Telephone CPR, first responder systems, cardiac arrest centers, and global campaigns are highlighted in the recent resuscitation guidelines. However, the degree of implementation is not yet sufficient. We do not only need to implement these measures, but we should also aim to monitor the systems regarding their performance and further improve them.