A single arm phase 2 clinical trial of YIV-906 with neoadjuvant concurrent chemo-radiation therapy in patients with locally advanced rectal cancer.

Background: Pre-operative chemoradiation for rectal cancer is often associated with severe gastrointestinal (GI) toxicity which can interrupt, delay, and/or lead to termination of treatment. In this study, we evaluated whether the addition of YIV-906, a novel herbal medicine proven to reduce GI toxicity associated with chemotherapy could also reduce GI side effects during standard pre-operative capecitabine and pelvic radiation therapy (RT) in the neoadjuvant setting for the treatment of locally advanced rectal cancer. Methods: This single arm clinical study enrolled 24 patients between Dec 23, 2014-Sep 17, 2018 at Smilow Cancer Hospital, a comprehensive cancer center at Yale New Haven Hospital. All patients were age ≥18 years, Eastern Cooperative Oncology Group 0-1 and with histologically confirmed T3-T4 and N0-N2, M0 adenocarcinoma of the rectum. Median follow-up was 61.9 months. All patients received concurrent pelvic external beam RT (50.4 Gy in 28 fractions), YIV-906 (taken orally 800 mg twice daily on days 1-4 of RT each week), and oral capecitabine delivered in a neo-adjuvant fashion, followed by definitive surgery. Toxicity was assessed weekly during radiation and until acute symptoms resolved and then at 28 days, 4 months, 7 months and 10 months. Toxicities were graded in accordance with Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Results: At the time of surgery, 4 patients (16.7%) had a complete or near-complete response. At a median follow-up of 61.9 months, the mean overall survival (OS) of our patient cohort was 74.9 months [95% confidence interval (CI): 67.3-82.5]. The estimated 5-year OS was 82.0%. We observed 0% acute grade 4 toxicities, and only two cases of acute grade 3 diarrhea (8.3%). Conclusions: The addition of YIV-906 to capecitabine based chemoradiation for locally advanced rectal cancer led to reduced rates of GI toxicity compared to historical controls, in particular grade 3 or greater diarrhea. These findings suggest YIV-906 should be evaluated in a randomized clinical trial to further assess potential reductions in the toxicity profile of chemoradiation for GI cancers.

Enhancing nursing students' clinical competency using a multi-patient simulation learning model: A randomized controlled study.

BACKGROUND: For nurses, clinical competency is paramount in ensuring that patients receive safe, high-quality care. Multi-patient simulation (MPS) in nursing education is gaining attention, and evidence shows its suitability for real-life situations. MPS can be an effective solution for nurses' continuing clinical education. OBJECTIVES: This project compares the effectiveness of MPS (involving both a standardized patient and a high fidelity simulator) and a single high-fidelity simulation (single HFS; only involving a high fidelity simulator) for enhancing the clinical competency of nursing students. DESIGN: A stratified, permuted, block randomized controlled study design was used. SETTINGS AND PARTICIPANTS: Sixty undergraduate nursing students in years 3, 4, and 5 were selected to participate. Subgroups with each comprising three undergraduate nursing students from different years were formed. METHODS: The participants were randomized to receive either an MPS (intervention group) or single HFS (control group) for 1 day; they later received the same intervention after a 30-day washout period. One objectively measured questionnaire and two self-reported questionnaires were used to measure clinical competency: the Creighton Competency Evaluation Instrument (CCEI), Clinical Competence Questionnaire (CCQ), and Simulation Effectiveness Tool - Modified Questionnaire (SET-M). RESULTS: The results revealed significant between-group differences. Specifically, the intervention group showed greater improvement than the control group in both the CCQ (linear contrast [d] = 71.4; 95 % confidence interval [CI] = 53.407, 89.393; P < 0.001) and CCEI total scores (d = 7.17; 95 % CI = 5.837, 8.503; P < 0.001). The SET-M results indicated that 85 % of the participants (n = 51) strongly agreed that they felt more confident about performing a patient handover to the healthcare team after the simulation. CONCLUSIONS: The study findings indicated that both the MPS and single HFS effectively enhanced students' clinical competency. However, MPSs have superior educational outcomes relative to traditional single HFSs.

Mesenchymal Stem Cell Exosomes Enhance Posterolateral Spinal Fusion in a Rat Model.

Spinal fusion, a common surgery performed for degenerative lumbar conditions, often uses recombinant human bone morphogenetic protein 2 (rhBMP-2) that is associated with adverse effects. Mesenchymal stromal/stem cells (MSCs) and their extracellular vesicles (EVs), particularly exosomes, have demonstrated efficacy in bone and cartilage repair. However, the efficacy of MSC exosomes in spinal fusion remains to be ascertained. This study investigates the fusion efficacy of MSC exosomes delivered via an absorbable collagen sponge packed in a poly Ɛ-caprolactone tricalcium phosphate (PCL-TCP) scaffold in a rat posterolateral spinal fusion model. Herein, it is shown that a single implantation of exosome-supplemented collagen sponge packed in PCL-TCP scaffold enhanced spinal fusion and improved mechanical stability by inducing bone formation and bridging between the transverse processes, as evidenced by significant improvements in fusion score and rate, bone structural parameters, histology, stiffness, and range of motion. This study demonstrates for the first time that MSC exosomes promote bone formation to enhance spinal fusion and mechanical stability in a rat model, supporting its translational potential for application in spinal fusion.

Increased matrix metalloproteinase-2 in ligamentum flavum hypertrophy and the regulation of MMP-2/TIMPs by elastin-derived peptides.

The study aimed to examine matrix metalloproteinase-2 (MMP-2) expression in a rat ligamentum flavum (LF) hypertrophy model in vivo, and the effect of elastin-derived peptides (EDPs) on MMP-2 and tissue inhibitors of metalloproteinases (TIMPs) in rat LF cells in vitro. Surgical destabilization was performed at the rat spinal L3/4 level to induce increased mechanical stress. Rats were killed at 6- and 12-weeks postsurgery for histological staining, immunohistochemical staining, RT-qPCR and western blot. 100 µg/mL EDPs were applied to isolated normal rat LF cells, with or without pretreatment of elastin receptor complex (ERC) inhibitors, to assess the expression of MMP-2, TIMP-1, and TIMP-2. Spinal destabilization led to LF hypertrophy, observed through increased LF thickness and area, along with histological changes of chondrometaplasia and elastic fiber degradation. LF was also stained positively for Col I and Col II, where elastic fiber has broken down. MMP-2 expression was notably elevated in the hypertrophied LF, accompanied by increased TIMP-2 and TIMP-3 levels. EDPs were found to suppress MMP-2 expression and reduce TIMP-1 and TIMP-2 levels in rat LF cells. Interestingly, exposure to EDPs led to a significant rise in MMP-2/TIMP-1 and MMP-2/TIMP-2 ratios, dependent on the ERC. Collectively, the study suggests that increased MMP-2 activity contributes to elastic fiber degradation in hypertrophied LF, generating EDPs that further enhance the MMP-2/TIMPs ratio in LF cells in an ERC-dependent manner. Further research is essential to delve into the mechanisms of EDPs in LF hypertrophy.

Non-pharmacological and pharmacological treatments for bone health after stroke: Systematic review with meta-analysis.

BACKGROUND: Hemi-osteoporosis is a common secondary complication of stroke. No systematic reviews of pharmacological and non-pharmacological agents for post-stroke bone health have estimated the magnitude and precision of effect sizes to guide better clinical practice. OBJECTIVES: To examine the benefits and harms of pharmacological and non-pharmacological agents on bone health in post-stroke individuals. METHODS: Eight databases were searched (PubMed, Cochrane library, Scopus, CINAHL Complete, Embase, PEDro, Clinicaltrils.gov and ICTRP) up to June 2023. Any controlled studies that applied physical exercise, supplements, or medications and measured bone-related outcomes in people with stroke were included. PEDro and the GRADE approach were used to examine the methodological quality of included articles and quality of evidence for outcomes. Effect sizes were calculated as standardized mean differences (SMD) and risk ratio (RR). Review Manager 5.4 was used for data synthetization. RESULTS: Twenty-four articles from 21 trials involving 22,500 participants (3,827 in 11 non-pharmacological and 18,673 in 10 pharmacological trials) were included. Eight trials were included in the meta-analysis. The methodological quality of half of the included non-pharmacological studies was either poor or fair, whereas it was good to excellent in 8 of 10 pharmacological studies. Meta-analysis revealed a beneficial effect of exercise on the bone mineral density (BMD) of the paretic hip (SMD: 0.50, 95 % CI: 0.16; 0.85; low-quality evidence). The effects of anti-resorptive medications on the BMD of the paretic hip were mixed and thus inconclusive (low-quality evidence). High-quality evidence showed that the administration of antidepressants increased the risk of fracture (RR: 2.36, 95 % CI 1.64-3.39). CONCLUSION: Exercise under supervision may be beneficial for hip bone health in post-stroke individuals. The effect of anti-resorptive medications on hip BMD is uncertain. The adverse effects of antidepressants on fracture risk among post-stroke individuals warrant further attention. Further high-quality studies are required to better understand this issue. REGISTRATION: PROSPERO CRD42022359186.

Biomechanical effects of foot orthoses on jump landing performance: A systematic review.

Jumping is involved in a wide range of sports and activities, and foot orthoses (FO) are suggested to enhance performance and prevent injury. The aim of this systematic review was to investigate whether using FO with different modifications affects jump landing biomechanics and improves performance in healthy individuals. The search strategy included 7 databases that identified 19 studies. The study quality was evaluated using a modified Downs and Black index. The primary outcome measures were joint kinematics, kinetics, muscle activity, vertical jump height, and horizontal jump distance. Our findings indicated that incorporating arch support with a rearfoot post and softer forefoot region into FO may improve several biomechanical variables during jump landing activities. Improvements in vertical ground reaction force loading rates, knee and ankle kinematics, and muscle cocontraction during jumping with FO could enhance jumping performance. In addition, improvements in hip, knee, ankle, and tibial kinematics and vertical ground reaction force loading rates during landing could reduce impact forces and related injuries. Although a limited number of studies have addressed the effects of FO on vertical jump height and horizontal jump distance, inserting such FO inside shoes with optimum bending stiffness could facilitate jumping performance. A rigorous exploration of the effect and mechanism of FO designs on jumping performance could benefit jumping-related activities and prevent ankle and knee injuries.

Effects of foot orthoses on running kinetics and kinematics: A systematic review and meta-analysis.

BACKGROUND: Foot orthoses (FOs) are often prescribed by clinicians to treat foot and ankle conditions, prevent running injuries, and enhance performance. However, the lack of higher-order synthesis of clinical trials makes it challenging for clinicians to adopt an evidence-based approach to FOs' prescriptions. RESEARCH QUESTION: Do FOs with different modifications alter lower extremity running kinematics and kinetics? METHODS: A systematic search of seven databases was conducted from inception to February 2023. The analysis was restricted to healthy adults without foot musculoskeletal impairments and studies that compared the FOs effects with the controls. The methodological quality of the 35 studies that met the eligibility criteria was evaluated using the modified Downs and Black checklist. The random effects model estimated the standardized mean difference (SMD) with 95% confidence intervals and effect sizes. Sub-group analyses based on FOs type were performed to assess the potential effects of the intervention. RESULTS: Our findings indicated that both custom and off-the-shelf arch-support FOs reduced peak plantar pressure at the medial heel (SMD=-0.35, and SMD=-1.03), lateral heel (SMD=-0.50, and SMD=-0.53), and medial forefoot (SMD=-0.20, and SMD=-0.27), but increased plantar pressure at the mid-foot (SMD=0.30, and SMD=0.56). Compared with the controls, significant increases (SMD=0.36) in perceived comfort were found with custom FOs. A reduction (SMD=-0.58) in initial ankle inversion was found when a raised heel cup was integrated with arch-support FOs. A medial post integrated with arch support exhibited a reduced ankle (SMD=-1.66) and tibial (SMD=-0.63) range of motion. Custom FOs, however, unfavorably affected the running economy (SMD=-0.25) and perceived exertion (SMD=0.20). SIGNIFICANCE: Although FOs have been reported to have some positive biomechanical effects in healthy populations without musculoskeletal impairments or running-related issues, they need to be optimized and generalized to achieve better running performance and prevent injury.

Examining the joint coordination during dynamic balance learning using vector coding and statistical parametric mapping analyses.

We aimed to examine the changes in balance performance, kinematic variables, and joint coordination of the lower extremities during the Y-balance learning task. Twenty female university students completed five consecutive blocks of Y-balance learning from days 3 to 7 (135 trials). Pre-tests and tests were performed on days 1 and 9. Maximum reach distance, peak joint angle, and joint coordination in the anterior (AL), posterolateral (PL), and posteromedial (PM) directions were measured to determine the efficacy of Y-balance performance. A repeated measures ANOVA was performed for the maximum reach distance across learning blocks to confirm whether learning had occurred. Our results indicated that the maximum reach distance on day 5 was longer than that on other learning days. The maximum reach distance significantly increased in the PL and PM directions after learning. The hip flexion (PL/PM), abduction (PM), internal rotation (PM), and external rotation (PL) angles increased after learning. The knee joint flexion angle increased in both AL and PL directions. Only the ankle dorsiflexion angle increased in the AL direction. Joint coordination indicated that the knee and hip joints performed simultaneously during internal rotation. Ankle-knee joint coordination was performed using dorsiflexion and flexion strategies. Statistical parametric mapping analysis indicated significant differences in the ankle sagittal plane in the AL direction, hip horizontal and hip/knee sagittal planes in the PL direction, and hip/knee sagittal and hip frontal/horizontal planes in the PM direction. These data suggest that the dynamic balance ability of the novice participants improved in relation to changes in coordination patterns after learning. The results of this study can be applied to other populations to improve their dynamic balance and prevent fall injuries.

Seeing through a robot's eyes: A cross-sectional exploratory study in developing a robotic screening technology for autism.

The present exploratory cross-sectional case-control study sought to develop a reliable and scalable screening tool for autism using a social robot. The robot HUMANE, installed with computer vision and linked with recognition technology, detected the direction of eye gaze of children. Children aged 3-8 (M = 5.52; N = 199) participated, 87 of whom had been confirmed with autism, 55 of whom were suspected to have autism, and 57 of whom were not considered to cause any concern for having autism. Before a session, a human experimenter instructed HUMANE to narrate a story to a child. HUMANE prompted the child to return his/her eye gaze to the robot if the child looked away, and praised the child when it re-established its eye gaze quickly after a prompt. The reliability of eye gaze detection was checked across all pairs of human raters and HUMANE and reached 0.90, indicating excellent interrater agreement. Using the pre-specified reference standard (Autism Spectrum Quotient), the sensitivity and specificity of the index tests (i.e., the number of robot prompts and duration of inattentiveness) reached 0.88 or above and the Diagnostic Odds Ratios were beyond 190. These results show that social robots may detect atypical eye patterns, suggesting a potential future for screening autism using social robots.

Greater foot and footwear mechanical work associated with less ankle joint work during running.

Footwear energy storage and return is often suggested as one explanation for metabolic energy savings when running in Advanced Athletic Footwear. However, there is no common understanding of how footwear energy storage and return facilitates changes in muscle and joint kinetics. The purpose of this study was to evaluate the magnitude and timing of foot, footwear and lower limb joint powers and work while running in Advanced and Traditional Athletic Footwear. Fifteen runners participated in an overground motion analysis study. Since footwear kinetics are methodologically challenging to quantify, we leveraged distal rearfoot power analyses ('foot + footwear' power) and evaluated changes in the magnitude and timing of foot + footwear power and lower limb joint powers. Running in Advanced Footwear resulted in greater foot + footwear work, compared to Traditional Shoes, and lower positive ankle work, potentially reducing the muscular demand on the runner. The timing of foot + footwear power varied only slightly across footwear. There are exciting innovation opportunities to manipulate the timing of footwear energy and return. This study demonstrates the research value of quantifying time-series foot + footwear power, and points industry developers towards footwear innovation opportunities.

Characteristics and outcome of a territory-wide cohort study of patients with acquired hemophilia A in Hong Kong.

INTRODUCTION: Acquired hemophilia A (AHA) is a rare bleeding disorder with destruction of factor VIII by autoantibodies. Comprehensive data for Chinese patients are lacking. Predictors of hospital stay have not been investigated. METHODS: A territory-wide review of patients diagnosed with AHA from January 1, 2012, to December 31, 2021 was performed by retrieving patients' information from an electronic database system in Hong Kong. RESULTS: Overall, 165 patients were included in this 10-year study, and the estimated incidence was 2.4 per million/year, which was higher than those reported from Caucasian cohorts. The median age of diagnosis was 80 years old. Patients had a long hospital stay (median: 25 days) and high mortality (55.2 %). The majority of deaths were caused by immunosuppression-related sepsis (49.5 %). Age was an independent predictor of overall survival (Hazard ratio: 1.065, 95 % CI: 1.037-1.093, p < 0.001), complete remission (CR) status (odd ratios (OR): 0.948, 95 % CI: 0.921-0.976, p < 0.001) and time to achieve CR (OR: 1.043, 95 % CI: 1.019-1.067, p < 0.001). Higher hemoglobin level on presentation was associated with shorter time to achieve CR (OR: 0.888, 95 % CI: 0.795-0.993, p = 0.037). Factor VIII level < 1 % normal, high inhibitor titer and intensive immunosuppressive regimen predicted long hospital stay. CONCLUSION: We presented comprehensive data of Chinese patients with AHA which comprised predominantly frail elderly who required long hospital stay and had high sepsis-related mortality. This posed challenges in managing AHA in such patients. Individualized immunosuppressive therapy is needed to balance the benefits and risk of septic complications.

YIV-818-A: a novel therapeutic agent in prostate cancer management through androgen receptor downregulation, glucocorticoid receptor inhibition, epigenetic regulation, and enhancement of apalutamide, darolutamide, and enzalutamide efficacy.

Introduction: Prostate cancer is the second leading cause of cancer death among men in the United States. Castration-Resistant Prostate Cancer (CRPC) often develops resistance to androgen deprivation therapy. Resistance in CRPC is often driven by AR variants and glucocorticoid receptor (GR). Thus, drugs that target both could be vital in overcoming resistance. Methods: Utilizing the STAR Drug Discovery Platform, three hundred medicinal plant extracts were examined across 25 signaling pathways to identify potential drug candidates. Effects of the botanical drug YIV-818-A, derived from optimized water extracts of Rubia cordifolia (R.C.), on Dihydrotestosterone (DHT) or Dexamethasone (DEX) induced luciferase activity were assessed in 22RV1 cells harboring the ARE luciferase reporter. Furthermore, the key active compounds in YIV-818-A were identified through activity guided purification. The inhibitory effects of YIV-818-A, RA-V, and RA-VII on AR and GR activities, their impact on AR target genes, and their roles in modifying epigenetic status were investigated. Finally, the synergistic effects of these compounds with established CRPC drugs were evaluated both in vitro and in vivo. Results: YIV-818-A was found to effectively inhibit DHT or DEX induced luciferase activity in 22RV1 cells. Deoxybouvardin (RA-V) was identified as the key active compound responsible for inhibiting AR and GR activities. Both YIV-818-A and RA-V, along with RA-VII, effectively downregulated AR and AR-V proteins through inhibiting protein synthesis, impacted the expression of AR target genes, and modified the epigenetic status by reducing levels of Bromodomain and Extra-Terminal proteins (Brd2/Brd4) and H3K27Ac. Furthermore, these compounds exhibited synergistic effects with apalutamide, darolutamide, or enzalutamide, and suppressed AR mediated luciferase activity of 22RV1 cells. Co-administration of YIV-818-A and enzalutamide led to a significant reduction of 22RV1 tumor growth in vivo. Different sources of R.C. had variable levels of RA-V, correlating with their potency in AR inhibition. Discussion: YIV-818-A, RA-V, and RA-VII show considerable promise in addressing drug resistance in CRPC by targeting both AR protein and GR function, along with modulation of vital epigenetic markers. Given the established safety profile of YIV-818-A, these findings suggest its potential as a chemopreventive agent and a robust anti-prostate cancer drug.

Inhibition of PLK4 remodels histone methylation and activates the immune response via the cGAS-STING pathway in TP53-mutated AML.

Acute myeloid leukemia (AML) with TP53 mutation is one of the most lethal cancers and portends an extremely poor prognosis. Based on in silico analyses of druggable genes and differential gene expression in TP53-mutated AML, we identified pololike kinase 4 (PLK4) as a novel therapeutic target and examined its expression, regulation, pathogenetic mechanisms, and therapeutic potential in TP53-mutated AML. PLK4 expression was suppressed by activated p53 signaling in TP53 wild-type AML and was increased in TP53-mutated AML cell lines and primary samples. Short-term PLK4 inhibition induced DNA damage and apoptosis in TP53 wild-type AML. Prolonged PLK4 inhibition suppressed the growth of TP53-mutated AML and was associated with DNA damage, apoptosis, senescence, polyploidy, and defective cytokinesis. A hitherto undescribed PLK4/PRMT5/EZH2/H3K27me3 axis was demonstrated in both TP53 wild-type and mutated AML, resulting in histone modification through PLK4-induced PRMT5 phosphorylation. In TP53-mutated AML, combined effects of histone modification and polyploidy activated the cGAS-STING pathway, leading to secretion of cytokines and chemokines and activation of macrophages and T cells upon coculture with AML cells. In vivo, PLK4 inhibition also induced cytokine and chemokine expression in mouse recipients, and its combination with anti-CD47 antibody, which inhibited the "don't-eat-me" signal in macrophages, synergistically reduced leukemic burden and prolonged animal survival. The study shed important light on the pathogenetic role of PLK4 and might lead to novel therapeutic strategies in TP53-mutated AML.

Right ventricular ejection fraction derived from intraoperative three-dimensional transesophageal echocardiography versus cardiac magnetic resonance imaging.

PURPOSE: Right ventricle (RV) assessment is critical during cardiac surgery. Traditional assessment consists of visual estimation and measurement of validated parameters. Cardiac magnetic resonance imaging (cMRI) is the gold standard for RV analysis, and transthoracic three-dimensional (3D) echocardiography is validated against this. We aimed to show that intraoperative 3D transesophageal echocardiography (TEE) RV assessment is feasible and can produce results that correlate with cMRI. METHODS: We recruited cardiac surgery patients who underwent cMRI within the preceding twelve preoperative months. An anesthetic protocol was followed pre-sternotomy and a 3D RV data set was acquired. We used TOMTEC 4D RV-Function to derive RV end-diastolic volume (EDV), end-systolic volume (ESV), and ejection fraction (EF). We compared these data with the corresponding MRI values. RESULTS: Twenty-five patients were included. Transesophageal echocardiography EDV and ESV differed from MRI measurements with a mean bias of -53 mL (95% confidence interval [CI], -80 to 26) and -21 mL (95% CI, -34 to -9). Transesophageal echocardiography EF did not differ significantly, with a mean bias of -4% (95% CI, -8 to 1). Results were unchanged after excluding MRIs older than 180 days. Correlation coefficients for EDV, ESV, and EF were r = 0.85, 0.91, and 0.80, respectively. Interclass correlation coefficients for EDV, ESV, and EF were 0.86, 0.89, and 0.96, respectively. CONCLUSIONS: Intraoperative TEE RV, EDV, and ESV are underestimated relative to cMRI because of analysis, anesthetic, and ventilation factors. The EF showed a low mean difference, and all values showed strong correlation with MRI. Reproducibility and feasibility were excellent and increased use in clinical practice should be considered.

RéSUMé: OBJECTIF: L'évaluation du ventricule droit (VD) est essentielle pendant la chirurgie cardiaque. L'évaluation traditionnelle consiste en une estimation visuelle et une mesure de paramètres validés. L'imagerie par résonance magnétique cardiaque (IRMc) est l'étalon-or pour l'analyse du VD, et l'échocardiographie transthoracique tridimensionnelle (3D) est validée par rapport cette modalité. Notre objectif était de démontrer que l'évaluation peropératoire du VD par l'échocardiographie transœsophagienne (ETO) était faisable et pouvait générer des résultats en corrélation avec l'IRMc. MéTHODE: Nous avons recruté des patient·es de chirurgie cardiaque ayant bénéficié d'une IRMc au cours des douze mois préopératoires précédents. Un protocole anesthésique a été suivi avant la sternotomie et un ensemble de données 3D sur le VD a été acquis. Nous avons utilisé le système TOMTEC 4D RV-Function pour calculer le volume télédiastolique (VTD), le volume télésystolique (VTS) et la fraction d'éjection (FE). Nous avons comparé ces données avec les valeurs correspondantes obtenues à l'IRM. RéSULTATS: Vingt-cinq personnes ont été incluses. Les valeurs de VTD et VTS obtenues à l'échocardiographie transœsophagienne différaient des mesures obtenues par IRM avec un biais moyen de ­53 mL (intervalle de confiance [IC] à 95 %, ­80 à 26) et ­21 mL (IC 95 %, ­34 à ­9). La FE obtenue par échocardiographie transœsophagienne ne différait pas significativement, avec un biais moyen de ­4 % (IC 95 %, ­8 à 1). Les résultats étaient inchangés après l'exclusion des IRM réalisés plus de 180 jours auparavant. Les coefficients de corrélation pour le VTD, le VTS et la FE étaient r = 0,85, 0,91 et 0,80, respectivement. Les coefficients de corrélation interclasse pour le VTD, le VTS et la FE étaient de 0,86, 0,89 et 0,96, respectivement. CONCLUSION: L'ETO peropératoire sous-estime les mesures du VD, du VTD et du VTS par rapport à l'IRMc en raison de facteurs d'analyse, d'anesthésie et de ventilation. La FE a montré une faible différence moyenne, et toutes les valeurs ont montré une forte corrélation avec l'IRM. La reproductibilité et la faisabilité étaient excellentes et une utilisation accrue dans la pratique clinique devrait être envisagée.

Benzodiazepine-Free Cardiac Anesthesia for Reduction of Postoperative Delirium (B-Free): A Protocol for a Multi-centre Randomized Cluster Crossover Trial.

Delirium is common after cardiac surgery and is associated with adverse outcomes. Administration of benzodiazepines before and after cardiac surgery is associated with delirium; guidelines recommend minimizing their use. Benzodiazepine administration during cardiac surgery remains common because of its recognized benefits. The Benzodiazepine-Free Cardiac Anesthesia for Reduction of Postoperative Delirium (B-Free) trial is a randomized cluster crossover trial evaluating whether an institutional policy of restricting intraoperative benzodiazepine administration (ie, ≥ 90% of patients do not receive benzodiazepines during cardiac surgery), as compared with a policy of liberal intraoperative benzodiazepine administration (ie, ≥ 90% of patients receive ≥ 0.03 mg/kg midazolam equivalent), reduces delirium. Hospitals performing ≥ 250 cardiac surgeries a year are included if their cardiac anesthesia group agrees to apply both benzodiazepine policies per their randomization, and patients are assessed for postoperative delirium every 12 hours in routine clinical care. Hospitals apply the restricted or liberal benzodiazepine policy during 12 to 18 crossover periods of 4 weeks each. Randomization for all periods takes place in advance of site startup; sites are notified of their allocated policy during the last week of each crossover period. Policies are applied to all patients undergoing cardiac surgery during the trial period. The primary outcome is the incidence of delirium at up to 72 hours after surgery. The B-Free trial will enroll ≥ 18,000 patients undergoing cardiac surgery at 20 hospitals across North America. Delirium is common after cardiac surgery, and benzodiazepines are associated with the occurrence of delirium. The B-Free trial will determine whether an institutional policy restricting the administration of benzodiazepines during cardiac surgery reduces the incidence of delirium after cardiac surgery. Clinicaltrials.gov registration number: NCT03928236 (First registered April 26, 2019).

L'état confusionnel est fréquent après une chirurgie cardiaque et il est associé à des complications. L'administration de benzodiazépines avant et après une chirurgie cardiaque est associée à l'état confusionnel; dans les lignes directrices, on recommande de réduire leur utilisation au minimum. L'administration de benzodiazépines pendant une chirurgie cardiaque demeure fréquente, en raison des leurs bienfaits reconnus. L'essai B-Free (Benzodiazepine-Free Cardiac Anesthesia for Reduction of Postoperative Delirium ou l'anesthésie sans benzodiazépine en contexte de chirurgie cardiaque pour la réduction de l'état confusionnel postopératoire) est un essai à répartition aléatoire par grappes et avec permutation, visant à évaluer si une politique institutionnelle de restriction de l'administration peropératoire de benzodiazépines (c.-à-d. que ≥ 90 % des patients ne reçoivent pas de benzodiazépines durant une chirurgie cardiaque) réduit l'état confusionnel, comparativement à une politique d'administration peropératoire libérale de benzodiazépines (c.-à-d. que ≥ 90 % des patients reçoivent ≥ 0,03 mg/kg d'équivalent du midazolam). Des hôpitaux effectuant au moins 250 chirurgies cardiaques par année sont inclus dans l'essai si leurs équipes d'anesthésie cardiaque acceptent d'appliquer les deux politiques relatives aux benzodiazépines en vertu de la répartition aléatoire et si les patients sont évalués toutes les 12 heures, en ce qui a trait à l'état confusionnel postopératoire, dans le cadre des soins cliniques habituels. Les hôpitaux mettent en œuvre la politique d'administration restreinte ou libérale de benzodiazépines durant 12 à 18 périodes de permutation de 4 semaines chacune. La répartition aléatoire de l'ensemble des périodes a lieu avant le début de l'essai à l'hôpital; les établissements sont avisés de la politique qui leur est attribuée au cours de la dernière semaine de chaque période de permutation. Les politiques sont appliquées à tous les patients qui subissent une chirurgie cardiaque durant la période de l'essai. Le critère d'évaluation principal est l'incidence de l'état confusionnel dans les 72 heures suivant l'intervention chirurgicale. L'étude B-Free inclura au moins 18 000 patients qui subiront une chirurgie cardiaque dans 20 hôpitaux en l'Amérique du Nord. L'état confusionnel est fréquent après une chirurgie cardiaque, et les benzodiazépines sont associées à la survenue de l'état confusionnel. L'essai B-Free permettra de déterminer si une politique institutionnelle de restriction de l'administration de benzodiazépines durant une chirurgie cardiaque réduit l'incidence de l'état confusionnel après une telle chirurgie.Clinicaltrials.gov registration number: NCT03928236 (First registered April 26, 2019).

A specific early eluting peak in Bio-Rad Variant II cation-exchange high-performance liquid chromatography (CE-HPLC) for the screening of alpha-thalassaemia in a Chinese population.

The early eluting peaks in the first minute of cation-exchange high-performance liquid chromatography (CE-HPLC) are often not analysed in haemoglobin pattern studies, except for haemoglobin (Hb) Bart's and Hb H peaks. In this study, we described the presence of a specific α-thalassaemia early eluting peak (αEEP) at the retention time of 0.24 min generated by Variant II CE-HPLC (ß-Thalassaemia Short Program; Bio-Rad Laboratories). We have evaluated the utility of αEEP for the screening of α-thalassaemia trait in our local Chinese population in comparison to the Hb H inclusion body test. A total of 303 blood samples presenting with microcytosis were sent for haemoglobin pattern study and were analysed for the presence or absence of αEEP and Hb H inclusions. Twenty cases with a normal mean corpuscular volume were assessed as a control. Discordant results between the αEEP and the Hb H inclusion test were reviewed with the α-globin genotyping test performed. The concordance rate of the αEEP and the Hb H inclusion body test was 96.0% (κ=0.921, p<0.001). Eight of 303 cases (2.6%) were initially negative for the Hb H inclusion test but positive for the αEEP. All eight cases were found to have occasional Hb H inclusion bodies upon review. Four of 303 cases (1.3%) were negative for the αEEP but positive for the Hb H inclusion test. Of these four cases, two (50%) showed heterozygous Southeast Asian (SEA) type deletion, one (25%) showed Hb Quong Sze mutation, and one (25%) showed no mutation detected upon molecular testing. All the Hb E trait cases with no Hb H inclusions and the negative control group showed the absence of the αEEP. The sensitivity and specificity of αEEP for detecting SEA deletion were 93.8% and 100% respectively, which is superior to the Hb H inclusion test (sensitivity 81.3%, specificity 95.2%). The αEEP is found to be a more sensitive method than the Hb H inclusion body test in the screening of α-thalassaemia trait in our Chinese population, in which SEA type deletion is prevalent. Further study is needed to explore the utility of the αEEP in the screening of α-thalassaemia traits in other populations. The exact nature of the αEEP is yet to be defined.