User Perceptions of Visual Clot in a High-Fidelity Simulation Study: Mixed Qualitative-Quantitative Study.

BACKGROUND: Viscoelastic hemostatic assays, such as rotational thromboelastometry (ROTEM) or thromboelastography, enable prompt diagnosis and accelerate targeted treatment. However, the complex interpretation of the results remains challenging. Visual Clot-a situation awareness-based visualization technology-was developed to assist clinicians in interpreting viscoelastic tests. OBJECTIVE: Following a previous high-fidelity simulation study, we analyzed users' perceptions of the technology, to identify its strengths and limitations from clinicians' perspectives. METHODS: This is a mixed qualitative-quantitative study consisting of interviews and a survey. After solving coagulation scenarios using Visual Clot in high-fidelity simulations, we interviewed anesthesia personnel about the perceived advantages and disadvantages of the new tool. We used a template approach to identify dominant themes in interview responses. From these themes, we defined 5 statements, which were then rated on Likert scales in a questionnaire. RESULTS: We interviewed 77 participants and 23 completed the survey. We identified 9 frequently mentioned topics by analyzing the interview responses. The most common themes were "positive design features," "intuitive and easy to learn," and "lack of a quantitative component." In the survey, 21 respondents agreed that Visual Clot is easy to learn and 16 respondents stated that a combination of Visual Clot and ROTEM would help them manage complex hemostatic situations. CONCLUSIONS: A group of anesthesia care providers found Visual Clot well-designed, intuitive, and easy to learn. Participants highlighted its usefulness in emergencies, especially for clinicians inexperienced in coagulation management. However, the lack of quantitative information is an area for improvement.

Divergent molecular networks program functionally distinct CD8+ skin-resident memory T cells.

Skin-resident CD8+ T cells include distinct interferon-γ-producing [tissue-resident memory T type 1 (TRM1)] and interleukin-17 (IL-17)-producing (TRM17) subsets that differentially contribute to immune responses. However, whether these populations use common mechanisms to establish tissue residence is unknown. In this work, we show that TRM1 and TRM17 cells navigate divergent trajectories to acquire tissue residency in the skin. TRM1 cells depend on a T-bet-Hobit-IL-15 axis, whereas TRM17 cells develop independently of these factors. Instead, c-Maf commands a tissue-resident program in TRM17 cells parallel to that induced by Hobit in TRM1 cells, with an ICOS-c-Maf-IL-7 axis pivotal to TRM17 cell commitment. Accordingly, by targeting this pathway, skin TRM17 cells can be ablated without compromising their TRM1 counterparts. Thus, skin-resident T cells rely on distinct molecular circuitries, which can be exploited to strategically modulate local immunity.

Coagulation Management of Critically Bleeding Patients With Viscoelastic Testing Presented as a 3D-Animated Blood Clot (The Visual Clot): Randomized Controlled High-Fidelity Simulation Study.

BACKGROUND: Guidelines recommend using viscoelastic coagulation tests to guide coagulation management, but interpreting the results remains challenging. Visual Clot, a 3D animated blood clot, facilitates interpretation through a user-centered and situation awareness-oriented design. OBJECTIVE: This study aims to compare the effects of Visual Clot versus conventional viscoelastic test results (rotational thrombelastometry [ROTEM] temograms) on the coagulation management performance of anesthesia teams in critical bleeding situations. METHODS: We conducted a prospective, randomized, high-fidelity simulation study in which anesthesia teams (consisting of a senior anesthesiologist, a resident anesthesiologist, and an anesthesia nurse) managed perioperative bleeding scenarios. Teams had either Visual Clot or ROTEM temograms available to perform targeted coagulation management. We analyzed the 15-minute simulations with post hoc video analysis. The primary outcome was correct targeted coagulation therapy. Secondary outcomes were time to targeted coagulation therapy, confidence, and workload. In addition, we have conducted a qualitative survey on user acceptance of Visual Clot. We used Poisson regression, Cox regression, and mixed logistic regression models, adjusted for various potential confounders, to analyze the data. RESULTS: We analyzed 59 simulations. Teams using Visual Clot were more likely to deliver the overall targeted coagulation therapy correctly (rate ratio 1.56, 95% CI 1.00-2.47; P=.05) and administer the first targeted coagulation product faster (hazard ratio 2.58, 95% CI 1.37-4.85; P=.003). In addition, participants showed higher decision confidence with Visual Clot (odds ratio 3.60, 95% CI 1.49-8.71; P=.005). We found no difference in workload (coefficient -0.03, 95% CI -3.08 to 2.88; P=.99). CONCLUSIONS: Using Visual Clot led to a more accurate and faster-targeted coagulation therapy than using ROTEM temograms. We suggest that relevant viscoelastic test manufacturers consider augmenting their complex result presentation with intuitive, easy-to-understand visualization to ease users' burden from unnecessary cognitive load and enhance patient care.

Patient Blood Management in Pregnancy.

Background: Patient blood management (PBM) is a multidisciplinary and patient-centered treatment approach, comprising the detection and treatment of anemia, the minimization of blood loss, and the rational use of allogeneic transfusions. Pregnancy, delivery, and the puerperium are associated with increased rates of iron deficiency and anemia, which correlates with worse maternal and fetal outcomes and places pregnant women at increased risk of obstetric hemorrhage. Summary: Early screening for iron deficiency before the onset of anemia, as well as the use of oral and intravenous iron to treat iron deficiency anemia, has been shown to be beneficial. Anemia in pregnancy and the puerperium should be treated according to a staged regimen, administering either iron alone or in combination with an off-label use of human recombinant erythropoietin in selected patients. This regimen should be tailored to the needs of each individual patient. Postpartum hemorrhage (PPH) accounts for up to one-third of maternal deaths in both developing and developed countries. Bleeding complications should be anticipated and blood loss reduced by interdisciplinary preventive measures and individually tailored care. It is recommended that facilities have a PPH algorithm, primarily focusing on prevention through use of uterotonics, but also incorporating early diagnosis of the cause of bleeding, optimization of hemostatic conditions, timely administration of tranexamic acid, and integration of point-of-care tests to support the guided substitution of coagulation factors, alongside standard laboratory tests. Additionally, cell salvage has proven beneficial and should be considered for various indications in obstetrics including hematologic disturbances, as well as various forms of placental disorders. Key Message: This article reviews PBM in pregnancy, delivery, and the puerperium. The concept comprises early screening and treatment of anemia and iron deficiency, a transfusion and coagulation algorithm during delivery, as well as cell salvage.

User Perceptions of ROTEM-Guided Haemostatic Resuscitation: A Mixed Qualitative-Quantitative Study.

Viscoelastic point-of-care haemostatic resuscitation methods, such as ROTEM or TEG, are crucial in deciding on time-efficient personalised coagulation interventions. International transfusion guidelines emphasise increased patient safety and reduced treatment costs. We analysed care providers' perceptions of ROTEM to identify perceived strengths and areas for improvement. We conducted a single-centre, mixed qualitative-quantitative study consisting of interviews followed by an online survey. Using a template approach, we first identified themes in the responses given by care providers about ROTEM. Later, the participants rated six statements based on the identified themes on five-point Likert scales in an online questionnaire. Seventy-seven participants were interviewed, and 52 completed the online survey. By analysing user perceptions, we identified ten themes. The most common positive theme was "high accuracy". The most common negative theme was "need for training". In the online survey, 94% of participants agreed that monitoring the real-time ROTEM temograms helps to initiate targeted treatment more quickly and 81% agreed that recurrent ROTEM training would be beneficial. Anaesthesia care providers found ROTEM to be accurate and quickly available to support decision-making in dynamic and complex haemostatic situations. However, clinicians identified that interpreting ROTEM is a complex and cognitively demanding task that requires significant training needs.

The impact of direct oral anticoagulants on viscoelastic testing - A systematic review.

Background: In case of bleeding patients and in acute care, the assessment of residual direct oral anticoagulant (DOAC) activity is essential for evaluating the potential impact on hemostasis, especially when a timely decision on urgent surgery or intervention is required. Viscoelastic tests are crucial in a modern goal-directed coagulation management to assess patients' coagulation status. However, the role of viscoelastic test to detect and quantify residual DOAC plasma levels is controversially discussed. The aim of this review was to systematically summarize the evidence of viscoelastic tests for the assessment of residual DOAC activity. Method: PubMed, Embase, Scopus, and the Cochrane Library were searched for original articles investigating the effect of rivaroxaban, apixaban, edoxaban, or dabigatran plasma levels on different viscoelastic tests of the adult population from database inception to December 31, 2021. Results: We included 53 studies from which 31 assessed rivaroxaban, 22 apixaban, six edoxaban, and 29 dabigatran. The performance of viscoelastic tests varied across DOACs and assays. DOAC specific assays are more sensitive than unspecific assays. The plasma concentration of rivaroxaban and dabigatran correlates strongly with the ROTEM EXTEM, ClotPro RVV-test or ECA-test clotting time (CT) and TEG 6s anti-factor Xa (AFXa) or direct thrombin inhibitor (DTI) channel reaction time (R). Results of clotting time (CT) and reaction time (R) within the normal range do not reliable exclude relevant residual DOAC plasma levels limiting the clinical utility of viscoelastic assays in this context. Conclusion: Viscoelastic test assays can provide fast and essential point-of-care information regarding DOAC activity, especially DOAC specific assays. The identification and quantification of residual DOAC plasma concentration with DOAC unspecific viscoelastic assays are not sensitive enough, compared to recommended anti-Xa activity laboratory measurements. Systematic review registration: [https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=320629], identifier [CRD42022320629].

Improved Task Performance, Low Workload, and User-Centered Design in Medical Diagnostic Equipment Enhance Decision Confidence of Anesthesia Providers: A Meta-Analysis and a Multicenter Online Survey.

Decision confidence­the subjective belief to have made the right decision­is central in planning actions in a complex environment such as the medical field. It is unclear by which factors it is influenced. We analyzed a pooled data set of eight studies and performed a multicenter online survey assessing anesthesiologists' opinions on decision confidence. By applying mixed models and using multiple imputation to determine the effect of missing values from the dataset on the results, we investigated how task performance, perceived workload, the utilization of user-centered medical diagnostic devices, job, work experience, and gender affected decision confidence. The odds of being confident increased with better task performance (OR: 1.27, 95% CI: 0.94 to 1.7; p = 0.12; after multiple imputation OR: 3.19, 95% CI: 2.29 to 4.45; p < 0.001) and when user-centered medical devices were used (OR: 5.01, 95% CI: 3.67 to 6.85; p < 0.001; after multiple imputation OR: 3.58, 95% CI: 2.65 to 4.85; p < 0.001). The odds of being confident decreased with higher perceived workload (OR: 0.94, 95% CI: 0.93 to 0.95; p < 0.001; after multiple imputation, OR: 0.94, 95% CI: 0.93 to 0.95; p < 0.001). Other factors, such as gender, job, or professional experience, did not affect decision confidence. Most anesthesiologists who participated in the online survey agreed that task performance (25 of 30; 83%), perceived workload (24 of 30; 80%), work experience (28 of 30; 93%), and job (21 of 30; 70%) influence decision confidence. Improved task performance, lower perceived workload, and user-centered design in medical equipment enhanced the decision confidence of anesthesia providers.

Faster Time to Treatment Decision of Viscoelastic Coagulation Test Results through Improved Perception with the Animated Visual Clot: A Multicenter Comparative Eye-Tracking Study.

As the interpretation of viscoelastic coagulation test results remains challenging, we created Visual Clot, an animated blood clot aiming to facilitate raw rotational thromboelastometry (ROTEM) parameters. This study investigated anesthesia personnel's cognitive processing in managing simulated bleeding scenarios using eye-tracking technology. This multicenter, international, computer-based study across five large, central European hospitals included 35 participants with minimal to no prior experience interpreting viscoelastic test results. Using eye-tracking technology and an iPad tagged with quick response codes, we defined the time to treatment decision and the time on screen surface in seconds of correctly solved scenarios as our outcomes. The median time to treatment decision was 52 s for Visual Clot and 205 s for ROTEM (p < 0.0001). The probability of solving the scenario correctly was more than 8 times higher when using Visual Clot than when using ROTEM (Hazard ratio [HR] 8.54, 95% CI from 6.5 to 11.21; p < 0.0001). Out of 194 correctly answered scenarios of participants with the eye-tracker, 154 (79.4%) were solved with Visual Clot and 40 (20.6%) with ROTEM. Participants spent on average 30 s less looking at the screen surface with Visual Clot compared to ROTEM (Coefficient −30.74 s, 95% CI from −39.27 to −22.27; p < 0.0001). For a comparison of the two modalities in terms of information transfer, we calculated the percentage of time on the screen surface of the overall time to treatment decision, which with Visual Clot was 14 percentage points shorter than with ROTEM (Coefficient −14.55, 95% CI from −20.05 to −9.12; p < 0.0001). Visual Clot seems to improve perception and detection of coagulopathies and leads to earlier initiation of the appropriate treatment. In a high-pressure working environment such as the operating and the resuscitation room, correct and timely decisions regarding bleeding management may have a relevant impact on patients' outcomes.

[Prehospital Pain Management: Overview and Potential Improvements]. / Präklinische Schmerztherapie: Übersicht und Verbesserungsmöglichkeiten.

Prehospital Pain Management: Overview and Potential Improvements Abstract. Pain is a frequent issue in the prehospital setting. Rapid and adequate analgesia has a positive effect on the physiological and psychological condition of patients. However, up to 43 % of patients still suffer insufficient analgesia. Several studies have identified some factors that contribute to this problem; these factors can be patient- and intervention-specific or dependent on the staff on duty. In order to improve prehospital analgesia in the future, structural and organizational changes as well as the implementation of new methods and therapies are essential.

Pre-eclampsia predictive ability of maternal miR-125b: a clinical and experimental study.

Pre-eclampsia (PE) is a systemic maternal syndrome affecting 2-8% of pregnancies worldwide and involving poor placental perfusion and impaired blood supply to the foetus. It manifests after the 20th week of pregnancy as new-onset hypertension and substantial proteinuria and is responsible for severe maternal and newborn morbidity and mortality. Identifying biomarkers that predict PE onset prior to its establishment would critically help treatment and attenuate outcome severity. MicroRNAs are ubiquitous gene expression modulators found in blood and tissues. Trophoblast cell surface antigen (Trop)-2 promotes cell growth and is involved in several cancers. We assessed the PE predictive ability of maternal miR-125b in the first trimester of pregnancy by measuring its plasma levels in women with normal pregnancies and with pregnancies complicated by PE on the 12th week of gestation. To gain insight into PE pathogenesis we investigated whether Trop-2 is targeted by miR-125b in placental tissue. Data analysis demonstrated a significant association between plasma miR-125b levels and PE, which together with maternal body mass index before pregnancy provided a predictive model with an area under the curve of 0.85 (95% confidence interval, 0.70-1.00). We also found that Trop-2 is a target of miR-125b in placental cells; its localization in the basal part of the syncytiotrophoblast plasma membrane suggests a role for it in the early onset of PE. Altogether, maternal miR-125b proved a promising early biomarker of PE, suggesting that it may be involved in placental development through its action on Trop-2 well before the clinical manifestations of PE.

Omega-3 fatty acids modulate the lipid profile, membrane architecture, and gene expression of leiomyoma cells.

Uterine leiomyomas (fibroids or myomas) are the most common benign tumors of premenopausal women and new medical treatments are needed. This study aimed to determine the effects of omega-3 fatty acids on the lipid profile, membrane architecture and gene expression patterns of extracellular matrix components (collagen1A1, fibronectin, versican, or activin A), mechanical signaling (integrin ß1, FAK, and AKAP13), sterol regulatory molecules (ABCG1, ABCA1, CAV1, and SREBF2), and mitochondrial enzyme (CYP11A1) in myometrial and leiomyoma cells. Myometrial tissues had a higher amount of arachidonic acid than leiomyoma tissues while leiomyoma tissues had a higher level of linoleic acid than myometrial tissues. Treatment of primary myometrial and leiomyoma cells with eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) reduced the monounsaturated fatty acid (MUFA) content and increased the polyunsaturated fatty acid (PUFA) content in both cell types. Myometrial and leiomyoma cell membranes were in the liquid-crystalline phase, but EPA- and DHA-treated cells had decreased membrane fluidity. While we found no changes in the mRNA expression of ECM components, EPA and DHA treatment reduced levels of ABCG1, ABCA1, and AKAP13 in both cell types. EPA and DHA also reduced FAK and CYP11A1 expression in myometrial cells. The ability of omega-3 fatty acids to remodel membrane architecture and downregulate the expression of genes involved in mechanical signaling and lipid accumulation in leiomyoma cells offers to further investigate this compound as preventive and/or therapeutic option.

The trophoblast cell surface antigen 2 and miR-125b axis in urothelial bladder cancer.

Human trophoblast cell surface antigen 2 (Trop-2) is a 40-kDa transmembrane glycoprotein that was first identified as a marker of human trophoblast cells. Trop-2 acts on cell proliferation, adhesion, and migration by activating a number of intracellular signalling pathways. Elevated Trop-2 expression has been demonstrated in several types of cancer and correlated with aggressiveness and poor prognosis. Since no data are available on Trop-2 in bladder cancer (BC), the purpose of the study was to determine its levels in tissue specimens from normal individuals and patients with BC at different stages. Moreover, since according to recent evidence Trop-2 is a miR-125b target, miR-125b expression was also assessed in tissue specimens. Finally, the effect of the Trop-2/miR-125b axis on the proliferation and migration of BC cells was evaluated in vitro. The Trop-2/miR-125b axis was seen to be differentially expressed in normal urothelium, non-invasive BC and invasive BC tissue. Significant miR-125b down-regulation was associated with a significant increase in Trop-2 protein levels in BC tissue and correlated with disease severity. In vitro analysis confirmed the role of miR-125b in down-modulation of Trop-2 protein levels and showed that Trop-2/miR-125b axis affects cellular proliferation in bladder tissue. In conclusion, our findings highlight a role for the Trop-2/miR-125b axis in BC progression and suggest Trop-2 and miR-125b as diagnostic/prognostic marker candidates as well as druggable targets for innovative therapeutic approaches.

CADASIL: Ultrastructural insights into the morphology of granular osmiophilic material.

INTRODUCTION: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary systemic vascular disorder. Granular osmiophilic material (GOM) is its ultrastructural marker. We reviewed tissue biopsies from CADASIL patients to establish whether ultrastructural observations help clarify the pathogenic mechanism of CADASIL. Given the resemblance of the GOM deposits to the immunoglobulin deposits seen in glomerulonephritis and focal segmental glomerulosclerosis (FSGS), their morphologies were investigated and compared. METHODS: Skin, skeletal muscle, kidney, and pericardium tissue biopsies from 13 patients with a clinical and molecular diagnosis of CADASIL, and kidney biopsies from five patients with IgA nephropathy and five patients with primary FSGS were subjected to ultrastructural examination. RESULTS: In CADASIL patients, several GOM deposits from all sites were partially or totally surrounded by an electron-lucent halo. The deposits frequently had a more electron-dense portion with a regular outline on the inner side and a less osmiophilic, looser outer side displaying a less regular profile. The uniformly dense deposits tended to be more osmiophilic if located close to the cell membrane and less osmiophilic if laid farther away from it. The immunoglobulin deposits from the glomerulonephritis and FSGS patients lacked both the granular pattern and the halo. CONCLUSIONS: This study demonstrates that GOM deposits may have a nonuniform morphology and describes in detail an electron-lucent halo surrounding several of them. It is conceivable that the halo is the morphological evidence and possibly the cause of an aberrant NOTCH3 processing, already suspected to be involved in CADASIL.

Locostatin, a disrupter of Raf kinase inhibitor protein, inhibits extracellular matrix production, proliferation, and migration in human uterine leiomyoma and myometrial cells.

OBJECTIVE: To investigate the presence of Raf kinase inhibitor protein (RKIP) in human myometrium and leiomyoma as well as to determine the effect of locostatin (RKIP inhibitor) on extracellular matrix (ECM) production, proliferation, and migration in human myometrial and leiomyoma cells. DESIGN: Laboratory study. SETTING: Human myometrium and leiomyoma. PATIENT(S): Thirty premenopausal women who were admitted to the hospital for myomectomy or hysterectomy. INTERVENTION(S): Myometrial and leiomyoma tissues were used to investigate the localization and the expression level of RKIP through immunohistochemistry and Western blotting. Myometrial and leiomyoma cells were treated with locostatin (10 µM) to measure ECM expression by real-time polymerase chain reaction, GSK3ß expression by Western blotting, cell migration by wound-healing assay, and cell proliferation by MTT assay and immunocytochemistry. MAIN OUTCOME MEASURE(S): The expression of RKIP in human myometrial and leiomyoma tissue; ECM components and GSK3ß expression, migration, and proliferation in myometrial and leiomyoma cells. RESULT(S): RKIP is expressed in human myometrial and leiomyoma tissue. Locostatin treatment resulted in the activation of the mitogen-activated protein kinase (MAPK) signal pathway (ERK phosphorylation), providing a powerful validation of our targeting protocol. Further, RKIP inhibition by locostatin reduces ECM components. Moreover, the inhibition of RKIP by locostatin impaired cell proliferation and migration in both leiomyoma and myometrial cells. Finally, locostatin treatment reduced GSK3ß expression. Therefore, even if the activation of MAPK pathway should increase proliferation and migration, the destabilization of GSK3ß leads to the reduction of proliferation and migration of myometrial and leiomyoma cells. CONCLUSION(S): Our results indicate that RKIP may be involved in leiomyoma pathophysiology.

Climbing Has a Positive Impact on Low Back Pain: A Prospective Randomized Controlled Trial.

OBJECTIVE: Comparison of climbing versus no treatment to treat chronic low back pain. DESIGN: Prospective randomized controlled trial. SETTING: Tertiary. PARTICIPANTS: A total of 30 patients with chronic low back pain were recruited and randomly assigned to 2 different groups: climbing and control. The inclusion criteria were defined as chronic low back pain, age between 18 and 45 years, body mass index lower than 25, and no climbing experience. INTERVENTIONS: Patients in the climbing group were instructed to climb 5 different climbing routes. A climbing activity of 10 sessions in 8 weeks, at least once a week with a minimum duration of 1 hour, was mandatory. MAIN OUTCOME MEASURES: The participants were examined before (T0) and after therapy (8 weeks, T8) and after another 6 weeks (T14). The outcome was evaluated using Oswestry Disability Index, Visual Analog Scale (VAS), Likert scale, and magnetic resonance imaging (MRI). Radiologists evaluating MRI were blinded. The study was performed as a single-center study. RESULTS: Evaluating the Oswestry Disability Index, a significant difference in the time course between the 2 groups was detected (P = 0.022). Significant improvements comparing climbing and control group were also found when assessing VAS in a minimal finger-floor-distance position (P = 0.048). Patients in the climbing group showed a reduction in size of disc protrusion. CONCLUSIONS: Climbing may be an effective and low-cost therapy option for people with chronic low back pain. CLINICAL RELEVANCE: Low back pain is a very common disease but still a challenge to treat. Therapy strategies vary from conservative ones, pharmacological treatment with non-steroidal anti-inflammatory drugs (NSAIDs) and weak opioids, to invasive treatment with acupuncture, injections, and operative reconstruction. Some can be costly and not without risks. For instance, many people who use NSAIDs are at risk of common side effects such as gastrointestinal complications (irritation, ulcers, and bleeding) that may lead to hospitalization. Climbing could offer reduction of pain and better performance in daily life, because it offers a closed chain muscle training that has the potential to improve posture, perception of the trunk midline, and muscle control. Climbing may also lead to a better adherence to continuing treatment than traditional physical therapy and exercise due to a more exciting aspect of the sports activity.