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.

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.

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.

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).

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.

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.

C-Reactive Protein as a Negative Predictive Marker for Anastomotic Leakage After Minimally Invasive Esophageal Surgery.

BACKGROUND: Serum C-reactive protein (CRP) is commonly used by surgeons to raise suspicion of anastomotic leakage and other infectious complications, but most studies on optimal cut-off values are retrospective with a small sample of patients. The aim of this study was to determine the accuracy and optimal cut-off value of CRP for anastomotic leakage in patients following esophagectomy for cancer. MATERIALS AND METHODS: Consecutive minimally invasive esophagectomy for esophageal cancer patients was included in this prospective study. Anastomotic leakage was confirmed if a defect or leakage of oral contrast was seen on a CT scan, by endoscopy or if saliva was draining from the neck incision. Diagnostic accuracy of CRP was assessed by receiver operator curve (ROC) analysis. Youden's index was adopted to determine the cut-off value. RESULTS: A total of 200 patients were included between 2016 and 2018. Postoperative day 5 showed the highest area under the ROC (0.825) and optimal cut-off value of 120 mg/L. This resulted in a sensitivity of 75%, specificity of 82%, negative predicting value of 97%, and positive predicting value of 32%. CONCLUSIONS: CRP on postoperative day 5 can be used as a negative predictor for and can be used as a marker to raise suspicion of anastomotic leakage following esophagectomy for esophageal cancer. When CRP exceeds 120 mg/L on postoperative day 5, additional investigations should be considered.

Perioperative Optimization of the Cardiac Surgical Patient.

Perioperative optimization of cardiac surgical patients is imperative to reduce complications, utilize health care resources efficiently, and improve patient recovery and quality of life. Standardized application of evidence-based best practices can lead to better outcomes. Although many practices should be applied universally to all patients, there are also opportunities along the surgical journey to identify patients who will benefit from additional interventions that will further ameliorate their recovery. Enhanced recovery programs aim to bundle several process elements in a standardized fashion to optimize outcomes after cardiac surgery. A foundational concept of enhanced recovery is attaining a better postsurgical end point for patients, in less time, through achievement and maintenance in their greatest possible physiologic, functional, and psychological state. Perioperative optimization is a broad topic, spanning multiple phases of care and involving a variety of medical specialties and nonphysician health care providers. In this review we highlight a variety of perioperative care topics, in which a comprehensive approach to patient care can lead to improved results for patients, providers, and the health care system. A particular focus on patient-centred care is included. Although existing evidence supports all of the elements reviewed, most require further improvements in implementation, as well as additional research, before their full potential and usefulness can be determined.

Redo heart transplant without allogeneic blood transfusion.

Allogeneic blood transfusion in cardiac surgery is associated with increased morbidity, mortality, and health care costs. We report a successful case of third-time redo sternotomy second-time redo heart transplantation without allogeneic blood transfusion owing to the multiple blood conservation strategies used throughout the perioperative period.

Activation of eIF4E-binding-protein-1 rescues mTORC1-induced sarcopenia by expanding lysosomal degradation capacity.

BACKGROUND: Chronic mTORC1 activation in skeletal muscle is linked with age-associated loss of muscle mass and strength, known as sarcopenia. Genetic activation of mTORC1 by conditionally ablating mTORC1 upstream inhibitor TSC1 in skeletal muscle accelerates sarcopenia development in adult mice. Conversely, genetic suppression of mTORC1 downstream effectors of protein synthesis delays sarcopenia in natural aging mice. mTORC1 promotes protein synthesis by activating ribosomal protein S6 kinases (S6Ks) and inhibiting eIF4E-binding proteins (4EBPs). Whole-body knockout of S6K1 or muscle-specific over-expression of a 4EBP1 mutant transgene (4EBP1mt), which is resistant to mTORC1-mediated inhibition, ameliorates muscle loss with age and preserves muscle function by enhancing mitochondria activities, despite both transgenic mice showing retarded muscle growth at a young age. Why repression of mTORC1-mediated protein synthesis can mitigate progressive muscle atrophy and dysfunction with age remains unclear. METHODS: Mice with myofiber-specific knockout of TSC1 (TSC1mKO), in which mTORC1 is hyperactivated in fully differentiated myofibers, were used as a mouse model of sarcopenia. To elucidate the role of mTORC1-mediated protein synthesis in regulating muscle mass and physiology, we bred the 4EBP1mt transgene or S6k1 floxed mice into the TSC1mKO mouse background to generate 4EBP1mt-TSC1mKO or S6K1-TSC1mKO mice, respectively. Functional and molecular analyses were performed to assess their role in sarcopenia development. RESULTS: Here, we show that 4EBP1mt-TSC1mKO, but not S6K1-TSC1mKO, preserved muscle mass (36.7% increase compared with TSC1mKO, P < 0.001) and strength (36.8% increase compared with TSC1mKO, P < 0.01) at the level of control mice. Mechanistically, 4EBP1 activation suppressed aberrant protein synthesis (two-fold reduction compared with TSC1mKO, P < 0.05) and restored autophagy flux without relieving mTORC1-mediated inhibition of ULK1, an upstream activator of autophagosome initiation. We discovered a previously unidentified phenotype of lysosomal failure in TSC1mKO mouse muscle, in which the lysosomal defect was also conserved in the naturally aged mouse muscle, whereas 4EBP1 activation enhanced lysosomal protease activities to compensate for impaired autophagy induced by mTORC1 hyperactivity. Consequently, 4EBP1 activation relieved oxidative stress to prevent toxic aggregate accumulation (0.5-fold reduction compared with TSC1mKO, P < 0.05) in muscle and restored mitochondrial homeostasis and function. CONCLUSIONS: We identify 4EBP1 as a communication hub coordinating protein synthesis and degradation to protect proteostasis, revealing therapeutic potential for activating lysosomal degradation to mitigate sarcopenia.

Development of an HPV Genotype Detection Platform Based on Aggregation-Induced Emission (AIE) and Flow-Through Hybridization Technologies.

Genetic mutations can cause life-threatening diseases such as cancers and sickle cell anemia. Gene detection is thus of importance for disease-risk prediction or early diagnosis and treatment. Apart from genetic defects, gene detection techniques can also be applied to gene-related diseases with high risk to human health such as human papillomavirus (HPV) infection. HPV infection has been strongly linked to cervical cancer. To achieve a high-throughput HPV gene detection platform, the flow-through hybridization system appears to be one of the commercialized diagnostic techniques for this purpose. The flow-through hybridization technique is based on a vacuum-guided flow of DNA fragments which is continuously directed toward the oligoprobes that are immobilized on the testing membrane. However, the conventional colorimetric method and signal read-out approach suffers a problem of low sensitivity. On the contrary, fluorescence approaches allow more sensitive detection and broad sensing ranges. In this work, a fluorescent dye HCAP, which possesses aggregation-induced emission (AIE) properties and is responsive to alkaline phosphatase, was developed and applied to the flow-through hybridization platform to achieve HPV genome diagnosis of clinical samples. Also, an automatic membrane reader was constructed based on the AIE-based diagnosis platform which can identify the diagnostic result of patient DNA with a total concordance rate of 100% in the clinical trial.

A combination of electroacupuncture and auricular acupuncture for postoperative pain after abdominal surgery for gynaecological diseases: A randomized controlled trial.

BACKGROUND: Postoperative pain following laparotomy for gynaecological diseases is a common problem that requires effective management to ensure patient satisfaction and recovery. Despite the wide use of acupuncture for pain management, knowledge of its efficacy in managing postoperative pain is limited. Previous literature used either acupuncture or auricular acupuncture alone. However, the combined use of acupuncture and auricular acupuncture have not been studied yet. PURPOSE: This study examined the efficacy and feasibility of combined electroacupuncture and auricular acupuncture compared to a sham control in reducing pain during 5 days after a laparotomy for gynaecological diseases. This combined therapy was hypothesized to provide greater pain reduction than previous studies with less frequent treatment. STUDY DESIGN: Randomized sham-controlled, patient- and- assessor-blinded trial. METHODS: This trial recruited 72 patients scheduled for laparotomy in Hong Kong. Either acupuncture (n = 36) or non-invasive sham acupuncture (n = 36) was performed on the patients preoperatively (1 session) and postoperatively (once a day, up to 6 sessions). The primary outcome was pain at rest, measured using a numerical rating scale from postoperative days 0-5. Secondary outcomes such as analgesics consumption were also assessed. A data and safety monitoring board (DSMB) was established. RESULTS: All 72 randomized patients were included in the analysis. The acupuncture group had a smaller pain score at rest at 22 hrs (mean = 2.6) than the sham control group (mean = 4.0) (Post hoc intention to treat analysis, Linear regression, mean difference = -1.4, 95% confidence interval = [-0.2] -2.7, p = 0.029). No statistically significant between-group difference was found in other outcomes. No serious adverse event was observed. CONCLUSION: Perioperative acupuncture treatments are safe and feasible, but the efficacy of acupuncture is inconclusive.

Left ventricular fibroma presenting as esophageal spasm: A case report.

Primary tumors of the heart are rare with fibromas most commonly identified in utero or infancy and rarely developing in adulthood. Patients with cardiac fibromas are often asymptomatic until tumor enlargement results in obstructive and nonspecific symptoms. A 39-year-old female presented with 5-year history of recurrent chest pain with functional dysphagia, indicative of esophageal spasm. Imaging identified a large left ventricular (LV) fibroma compressing the esophagus provoking esophageal spasm. The fibroma was excised measuring 51 × 39 mm. This case describes presentation with esophageal spasm, contributing a novel presentation of LV fibroma to the literature.

Health Risks and Musculoskeletal Problems of Elite Mobile Esports Players: a Cross-Sectional Descriptive Study.

BACKGROUND: Mobile-gaming athletes sit in the same posture for prolonged periods, contributing to significant health risks. This study investigated the health profiles, fatigue, pain and complaints, and musculoskeletal problems of full-time mobile-gaming athletes. METHODS: A total of 50 elite mobile-gaming athletes were involved in this study. They were the starting lineup players from all ten professional teams competing in a top-tier multiplayer online battle arena tournament. A survey was conducted to evaluate their fatigue patterns, pain levels, and complaints. A descriptive analysis was conducted to evaluate the athletes' health profiles [body mass index (BMI), fat ratio], fatigue, number of complaints, and musculoskeletal problems. The associations of career duration with BMI, fat ratio, and the total number of confirmed injuries were then determined using Spearman's rank correlation test. RESULTS: A total of 46% and 44% of the participants felt tired frequently and occasionally, while 34% and 58% experienced eyestrain frequently and occasionally, respectively. More than 30% of the participants reported headache and rhinitis. A longer esports career duration was associated with a reduction in BMI (r = -0.272, p = 0.056). Career duration had no significant association with smoking habits (p = 0.666), alcohol habits (p = 0.655), coffee habits (p = 0.946), rounds of games for which the player could maintain concentration (p = 0.253), ease of eyestrain (p = 0.569), tiredness (p = 0.510), dizziness (p = 0.071), or leg numbness (p = 0.318). CONCLUSION: The findings of this study stress the significance of esports injuries and indicate preventive measures for both athletes and recreational players.

Resolution of platelet count interference due to cytoplasmic fragments of leukaemic cells by flow cytometry in acute myeloid leukaemia.

BACKGROUND: Platelet count interference could lead to problems in clinical decisions especially in the cases of thrombocytopenia. Here we report a case of platelet count interference in Beckman Coulter DxH800 haematology analyser due to cytoplasmic fragments of leukaemic cells in acute myeloid leukaemia. A 19-year-old female patient presented to the emergency department with bruises and anaemic symptoms. A machine platelet count (by impedance method) was 40 × 109 /L. There was a flag on platelet count interference by debris. Peripheral blood smear showed some bluish cytoplasmic fragments are seen mimicking platelets. METHOD: Immunological platelet counting by flow cytometry using fluorochrome-labeled antibodies against platelet markers CD41 and CD61 was attempted by adopting and modifying from the ICSH reference method for platelet counting. Events with low forward scatter and positive CD41 and/or CD61 expression were identified as platelets, and events with high forward scatter and negative CD41 and CD61 expression were identified as red cells. RESULTS: The platelet count was derived from the formula: Platelet count = RBC count (Haematology analyser) × PLT event (flow cytometry)/RBC events (flow cytometry). The immunological platelet count was determined to be 2 × 109 /L, which is much lower than the original machine count and platelet transfusion was warranted.

Regulation of proton partitioning in kinase-activating acute myeloid leukemia and its therapeutic implication.

Gain-of-function kinase mutations are common in AML and usually portend an inferior prognosis. We reported a novel mechanism whereby kinase mutants induced intracellular alkalization characteristic in oncogenesis. Thirteen kinases were found to activate sodium/hydrogen exchanger (NHE1) in normal hematopoietic progenitors, of which FLT3-ITD, KRASG12D, and BTK phosphorylated NHE1 maintained alkaline intracellular pH (pHi) and supported survival of AML cells. Primary AML samples with kinase mutations also showed increased NHE1 phosphorylation and evidence of NHE1 addiction. Amiloride enhanced anti-leukemic effects and intracellular distribution of kinase inhibitors and chemotherapy. Co-inhibition of NHE1 and kinase synergistically acidified pHi in leukemia and inhibited its growth in vivo. Plasma from patients taking amiloride for diuresis reduced pHi of leukemia and enhanced cytotoxic effects of kinase inhibitors and chemotherapy in vitro. NHE1-mediated intracellular alkalization played a key pathogenetic role in transmitting the proliferative signal from mutated-kinase and could be exploited for therapeutic intervention in AML.

Valve-in-Valve Using Perceval Prostheses for Prosthetic Valve Endocarditis.

Surgical treatment for prosthetic valve endocarditis remains a challenge. Rapid deployment valves have emerged as an option in the redo setting for infective endocarditis and in patients with a small or calcified aortic root. This report presents 3 patients with prosthetic valve endocarditis who underwent redo aortic valve replacement with the Perceval (LivaNova) prosthesis using the valve-in-valve technique. Hemodynamic performance of the prostheses was excellent during the perioperative period and at follow-up.