Antidote Research Articles

Association of Fentanyl Test Strip Use, Perceived Overdose Risk, and Naloxone Possession among People Who Use Drugs

Background: As opioid overdoses continue rising, interventions are needed to expand naloxone carriage, an opioid overdose reversal agent. Use of fentanyl test strips (FTS) might promote naloxone carriage. This study examines the relationship between FTS use, perceived overdose risk, and naloxone carriage in Wisconsin, United States. Methods: In a survey of people who use drugs (n = 341) in southern Wisconsin, respondents were asked about FTS use, perceived overdose risk, and how often they (1) have naloxone, (2) have more than one dose of naloxone, and (3) the number of naloxone doses possessed currently. Likert responses were mapped to an integer scale. Ordinal and linear multivariable regression examined the relationship between FTS use and study outcomes while adjusting for respondent characteristics. Results: Most respondents were male (59.6%), identified heroin as their drug of choice (70.7%) and reported intravenous use (87.9%). In unadjusted models, FTS use was associated with more often having naloxone (OR: 2.10; p = 0.005), more often having multiple naloxone doses (OR: 2.98; p < 0.001), and possessing a greater number of naloxone doses (dose count difference: 2.85; p = 0.001). In adjusted models, FTS use was associated with more often having multiple naloxone doses (OR: 2.29; p = 0.005) and possessing a greater number of naloxone doses (dose count difference: 2.25, p = 0.020). Conclusions: Individuals who use FTS more often carry multiple doses relative to individuals who do not use FTS. Given that naloxone carriage is critical for reducing opioid overdose risk, expanding FTS use may offer a strategy to reduce opioid overdose rates via improved naloxone carriage.

PB0366 Ticagrelor Overdose Managed without Adverse Outcomes: Is Reversal Agent Necessary?

PB0366 Ticagrelor Overdose Managed without Adverse Outcomes: Is Reversal Agent Necessary?

When reversal agent goes wrong – anaphylaxis with sugammadex

When reversal agent goes wrong – anaphylaxis with sugammadex

The implications of antithrombotic agents on subdural hematoma evacuation: what does "reversal" truly entail?

The optimal perioperative management of antithrombotic therapy (ATT) in patients requiring urgent neurosurgical intervention for subdural hematoma (SDH) is poorly understood. The delicate equilibrium of effective hemostasis while preventing thrombosis is complex and relies on numerous factors such as indication for and type of ATT, medical comorbidities, and extent of neurological injury. This study aimed to analyze the impact of ATT and reversal strategies on surgical outcomes to highlight current challenges in the management of these high-risk patients. The authors performed a retrospective surgical cohort analysis of 100 patients undergoing urgent SDH evacuation at a level I trauma center between March 2020 and May 2021. The patients were first stratified into two cohorts based on preoperative ATT use and then further segregated by receipt of reversal agents. Statistical analysis included the chi-square test, Welch two-sample t-test, and multivariate logistic regression. The primary outcome was mortality. Secondary endpoints included radiographic SDH reexpansion, revision surgery, improvement in preoperative neurological deficits, and incidence of thromboembolism. A crossover cohort was secondarily analyzed in patients for whom ATT was interrupted for a minimum duration equal to effective drug metabolism. Finally, ATT reinitiation patterns were examined. Of 100 patients, 48% received ATT, 54.2% of whom were given reversal agents. ATT use was significantly associated with decreased rates of postoperative neurological improvement (p = 0.023) with trends toward increased mortality (p = 0.078), SDH reexpansion (p = 0.12), and need for revision surgery (p = 0.10). Patient crossover revealed a 4 times greater likelihood of death in patients without ATT interruption prior to surgery (p = 0.040) without an observable impact on secondary outcomes. ATT reversal contributed no improvement in outcomes other than a decreased intensive care unit length of stay when adjusted for in-hospital mortality (p = 0.014). The rate of postoperative thromboembolism following ATT reversal was 11.5%. ATT reinitiation was highly variable, occurring in 59.5% of patients, with median times of 17 and 15 days for antiplatelets and anticoagulants, respectively. Use of preoperative ATT portends poor clinical outcomes following nonelective SDH evacuation regardless of attempts to reverse these medications with replacement blood products. This study further reinforces the critical need for judicious use of ATT and optimization of reversal strategies in high-risk patient populations as best guided by multidisciplinary teams and evolving clinical practice guidelines.

Investigation and Application of Reversible Temporary Plugging Steering Agent for Acidification

In order to solve the problems of insolubility of conventional plant gum type solid steering agents and the need to return after stratified acidification to unblock the formation, two chemically reversible temporary plugging agents were developed in this paper. The variation of viscosity of liquid steering agent and the dissolution of particles of solid-liquid combination steering agent were evaluated indoors. The liquid steering agent single-pipe core blocking experiment and double-pipe core splitting rate experiment were carried out, and the indoor over-hole plate pressure measurement experiments of different types of steering agents were conducted. And the two steering agents were applied in the field. The results show that the viscosity of liquid steering agent can change with the pH value, showing the characteristics of becoming viscous in acid and decomposing in water, which can increase the injection pressure by 1.95MPa after plugging the core in the indoor experiment, and can increase the construction pressure by 1.4MPa in the field application. What’s more, the pressure of solid-liquid combination steering agent indoor over pore plate is 3 times of liquid temporary plugging agent, and the construction pressure can be increased by 3.0 MPa. Both of the above temporary plugging agents can be dissolved by themselves in the process of water injection after the measure, and the plugging of the reservoir can be released without returning to the drainage. Meanwhile, it can also meet the needs of different pressure difference layer section for diversion acidification.

PB0033 Validated in vivo Model to Assess Direct Oral Anticoagulant Reversal Agents

PB0033 Validated in vivo Model to Assess Direct Oral Anticoagulant Reversal Agents

Oral Anticoagulants Beyond Warfarin.

Direct oral anticoagulants (DOACs) have largely replaced vitamin K antagonists, mostly warfarin, for the main indications for oral anticoagulation, prevention and treatment of venous thromboembolism, and prevention of embolic stroke in atrial fibrillation. While DOACs offer practical, fixed-dose anticoagulation in many patients, specific restrictions or contraindications may apply. DOACs are not sufficiently effective in high-thrombotic risk conditions such as antiphospholipid syndrome and mechanical heart valves. Patients with cancer-associated thrombosis may benefit from DOACs, but the bleeding risk, particularly in those with gastrointestinal or urogenital tumors, must be carefully weighed. In patients with frailty, excess body weight, and/or moderate-to-severe chronic kidney disease, DOACs must be cautiously administered and may require laboratory monitoring. Reversal agents have been developed and approved for life-threatening bleeding. In addition, the clinical testing of potentially safer anticoagulants such as factor XI(a) inhibitors is important to further optimize anticoagulant therapy in an increasingly elderly and frail population worldwide.

Self-Adjuvanting TLR7/8 Agonist and Fentanyl Hapten Co-Conjugate Achieves Enhanced Protection against Fentanyl Challenge.

Currently approved pharmacotherapies for opioid use disorders (OUDs) and overdose reversal agents are insufficient to slow the spread of OUDs due to the proliferation of fentanyl. This is evident in the 31% rise in drug overdose deaths from 2019 to 2022, with rates increasing from 21.6 to 28.3 overdoses per 100,000 deaths. Vaccines are a potential alternative or adjunct therapy for the treatment of several substance use disorders (nicotine, cocaine) but have shown limited clinical success due to suboptimal antibody titers. In this study, we demonstrate that coconjugation of a Toll-like receptor 7/8 (TLR7/8) agonist (UM-3006) alongside a fentanyl-based hapten (F1) on the surface of the carrier protein cross-reactive material 197 (CRM) significantly increased generation of high-affinity fentanyl-specific antibodies. This demonstrated enhanced protection against fentanyl challenges relative to an unconjugated (admix) adjuvant control in mice. Inclusion of aluminum hydroxide (alum) adjuvant further increased titers and enhanced protection, as determined by analysis of fentanyl concentration in serum and brain tissue. Collectively, our findings present a promising approach to enhance the efficacy of antiopioid vaccines, underscoring the need for extensive exploration of TLR7/8 agonist conjugates as a compelling strategy to combat opioid use disorders.

Sugammadex: A Milestone that Brings Changes in Anesthesia Practice

Sugammadex is a modified form of gamma-cyclodextrin that reverses the effects of rocuronium and vecuronium, which are aminosteroid non-depolarizing muscle relaxants (NDMR). It is the first and only reversal agent in the class of selective relaxant binding agents (SRBA) that reverses any depth of neuromuscular blockade without the unwanted muscarinic side effects of neostigmine (bronchospasm, nausea, vomiting, bradycardia, diarrhea, etc.) and anti-muscarinic side effects of glycopyrrolate (dry mouth, palpitations, urinary retention, constipation, etc.). It is an Food and Drug Administration (FDA)-approved agent that is safe for the reversal of neuromuscular block (NMB) caused by rocuronium and is available worldwide. Sugammadex practical use is predicted to alleviate many of the faults in present anesthetic practice regarding the antagonistic effects of rocuronium and other aminosteroid muscle relaxants. Despite being a novel agent in the reversal of NMB, the cost of sugammadex may limit its use as a regular antagonist of neuromuscular-blocking drugs.

Cycloartane-type triterpenoids and steroids from Trichilia connaroides and their multidrug resistance reversal activities

Four undescribed cycloartane-type triterpenoids (1−4) and seven undescribed steroids (6−12), along with five known analogues (5 and 13−16), were isolated from the leaves of Trichilia connaroides. Their structures were identified based on the NMR data and HRESIMS, and the absolute configurations were determined through single-crystal X-ray diffraction analysis, Mosher's method, and ECD calculations. The multidrug resistance (MDR) reversal activities of all the isolates were assessed, and compounds 10 and 11 showed significant activities to reverse the MDR of MCF-7/DOX cells with IC50 values of 2.90 and 3.76 μM, respectively. These bioactive compounds may bring fresh insights into the research and development of MDR reversal agents.

Micropatterned primary hepatocyte co-culture (HEPATOPAC) for fatty liver disease modeling and drug screening

Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent, progressive disorder and growing public health concern. To address this issue considerable research has been undertaken in pursuit of new NAFLD therapeutics. Development of effective, high-throughput in vitro models is an important aspect of drug discovery. Here, a micropatterned hepatocyte co-culture (MPCC) was used to model liver steatosis. The MPCC model (HEPATOPACTM) is comprised of hepatocytes and 3T3-J2 mouse stromal cells plated onto a patterned standard 96-well or 24-well plate, allowing the cultures to be handled and imaged in a standardized multi-well format. These studies employed high content imaging (HCI) analysis to assess lipid content in cultures. HCI analysis of lipid accumulation allows large numbers of samples to be imaged and analyzed in a relatively short period of time compared to manual acquisition and analysis methods. Treatment of MPCC with free fatty acids (FFA), high glucose and fructose (HGF), or a combination of both induces hepatic steatosis. MPCC treatment with ACC1/ACC2 inhibitors, as either a preventative or reversal agent, showed efficacy against FFA induced hepatic steatosis. Drug induced steatosis was also evaluated. Treatment with valproic acid showed steatosis induction in a lean background, which was significantly potentiated in a fatty liver background. Additionally, these media treatments changed expression of fatty liver related genes. Treatment of MPCC with FFA, HGF, or a combination reversibly altered expression of genes involved in fatty acid metabolism, insulin signaling, and lipid transport. Together, these data demonstrate that MPCC is an easy to use, long-term functional in vitro model of NAFLD having utility for compound screening, drug toxicity evaluation, and assessment of gene regulation.

The latency-reversing agent HODHBt synergizes with IL-15 to enhance cytotoxic function of HIV-specific T cells.

IL-15 is under clinical investigation toward the goal of curing HIV infection because of its abilities to reverse HIV latency and enhance immune effector function. However, increased potency through combination with other agents may be needed. 3-Hydroxy-1,2,3-benzotriazin-4(3H)-one (HODHBt) enhances IL-15-mediated latency reversal and NK cell function by increasing STAT5 activation. We hypothesized that HODHBt would also synergize with IL-15, via STAT5, to directly enhance HIV-specific cytotoxic T cell responses. We showed that ex vivo IL-15 + HODHBt treatment markedly enhanced HIV-specific granzyme B-releasing T cell responses in PBMCs from antiretroviral therapy-suppressed (ART-suppressed) donors. We also observed upregulation of antigen processing and presentation in CD4+ T cells and increased surface MHC-I. In ex vivo PBMCs, IL-15 + HODHBt was sufficient to reduce intact proviruses in 1 of 3 ART-suppressed donors. Our findings reveal the potential for second-generation IL-15 studies incorporating HODHBt-like therapeutics. Iterative studies layering on additional latency reversal or other agents are needed to achieve consistent ex vivo reservoir reductions.

Implementation Status and Challenges Associated With Implementation of the Targeted Medication Safety Best Practices in a Tertiary Hospital.

Background The Institute for Safe Medication Practices (ISMP) is a well-known non-profit organization dedicated to preventing medication errors. Every two years they publish best practices that can reduce the occurrence of medication errors. This study aims to evaluate the implementation status of these best practices and to understand barriers associated with non-implementation at a tertiary hospital in Saudi Arabia. Methodology This was a two-phase qualitative study. First, a survey consisting of the ISMP best practices was sent to employees (mainly heads of departments) to fill out the implementation rate for each best practice. Then an interview or a focus group was conducted to further validate their answers and understand why some best practices were not implemented. Results Our study found that the highest implemented best practices were having strategies to improve safety with high-alert medications (best practice #19, 85.7%), having antidotes and reversal agents readily available (best practice #9, 75%), independent verification of sterile preparation (best practice #11, 75%), and limiting the number of removable medications from the automated dispensing unit by override (best practice #16, 75%). The least implemented best practices were ensuring that oral liquid medications are dispensed in a syringe (best practice #4, 12.5%), maximizing use of barcode verification (best practice #18, 12.5%), purchasing oral liquid dosing devices that display metric scale (best practice #5, 25%), eliminating glacial acetic acid from all areas of the hospital (best practice #6, 28.6%), and eliminating all 1,000 mL of sterile water from all areas outside of the pharmacy (best practice #10, 28.6%). Challenges associated with implementation were related to knowledge, motivation, and opportunity in the environment, with the latter being the highest barrier associated with non-implementation. Conclusions Healthcare providers need to have knowledge about the best practices and the rationale behind them, the motivation to perform them, and the necessary resources to implement the best practices in their hospital.

Propensity of use of neuromuscular blocking agents among Indian anaesthesiologists: A questionnaire-based survey

This survey aimed to understand the use of neuromuscular blockers (NMBs) with respect to neuromuscular monitoring, reversal of residual neuromuscular block, and incidence of adverse events among Indian anaesthesiologists.A 40-item questionnaire was sent to 250 anaesthesiologists across India via email and their responses were statistically analysed.The response rate was 50%. To facilitate tracheal intubation, 81.0% respondents preferred cisatracurium, 72.2% preferred atracurium, 43.7% preferred vecuronium, 58.7% preferred rocuronium, and 70.6% preferred succinylcholine. Safety and recovery time are the most important criteria for an ideal NMB. About 84% respondents expressed concerns about the adverse effects of NMBs, especially recovery of neuromuscular function (31.1%) and hemodynamic effects (26.4%). The train-of-four (TOF) ratio for residual paralysis was not checked by 57% respondents. Reversal agents were used by &amp;#62;2/3 respondents; however, 86.5% used them after cisatracurium was used. Concerns about adverse effects of anticholinesterase/antimuscarinic agents were expressed by 63.4% respondents, while 85% expressed the need for availability of sugammadex in India. Almost two-thirds opined that conventional nerve stimulators and quantitative TOF monitors should be available in the operating room.The survey showed that safety and recovery time are the most important parameters in selecting an NMB. Cisatracurium was the most widely used NMB for tracheal intubation because of its safety, duration of action, less anaphylactic reactions, and fewer hemodynamic fluctuations. The use of TOF for monitoring was low. While reversal agents were used by &amp;#62;2/3 respondents, many respondents used them after cisatracurium was used as an NMB.

221 A one-year audit of intracranial haemorrhages that presented to a level 4 hospital and died within 30 days

Abstract Background Spontaneous Intra-Cerebral Haemorrhage (ICH) constitutes 15% of all strokes and has a 1 month mortality of 40%. Different prognostic models are used but the most widely used model is the ICH score. Predictors for 30-day mortality include greater ICH volume, infratentorial location of ICH, low Glasgow Coma Scale (GCS), older age, and intraventricular extension. We audited all non-traumatic ICH that presented to a level 4 Hospital and died within 30 days in 2021. Methods We retrospectively collected all adult patients with imaging-confirmed (CT- or MRI-scan) non-traumatic ICH and died within 30 days. Patients were identified via FAST Call register. Exclusion criteria were traumatic ICH or non-parenchymal haemorrhage, haemorrhagic transformation of ischemic stroke, brain tumour associated haemorrhage. Data included age, GCS on admission, co-morbidities, Modified Rankin Score (MRS) pre admission, oral anticoagulation/anti-platelet use/time, patient’s blood pressure recordings. If the patient was referred to Neurosurgery, advice was collated. Haemorrhagic properties were measured on CT: supra- or infratentorial, intraventricular extension, and ICH volume (ABC/2 method). ICH Scores were calculated. Results 29 ICH were identified with a 30 day mortality of 37.9%(11/29) and a mean age of 80.9 years. Median-MRS pre-admission was 3, GCS on arrival was 9(3–13). 5/11(45%) were admitted to the Stroke Unit. 5 patients were on anticoagulation and 3 received a reversal agent. 8 patients had a systolic BP 150-220 mmHg on arrival of whom 3/8(38%) achieved a target BP of ≤140 mmHg at 2 hours of diagnosis. Mean volume of ICH was 45.6mls. Median ICH score was 3. Conclusion 29 patients presented with an ICH with a 30 day mortality of 37.9%. These were frail and multi-morbid patients. 45% were admitted to the stroke unit and 38% achieved optimal blood pressure control within 2 hours. This highlight two areas that could be improved to ensure optimum patient care.

Risk Factors for Postoperative Urinary Retention After Lumbar Fusion Surgery: Anesthetics and Surgical Approach.

Postoperative urinary retention (POUR) after lumbar fusion surgery can lead to longer hospital stays and thus increased risk of developing other postoperative complications. Therefore, we aimed to determine the relationship between POUR and (1) surgical approach and (2) anesthetic agents, including sugammadex and glycopyrrolate. After institutional review board approval, L4-S1 single-level lumbar fusion surgeries between 2018 and 2021 were identified. A 3:1 propensity match of patients with POUR to those without was conducted, controlling for patient age, sex, diabetes status, body mass index, smoking status, history of benign prostatic hyperplasia, and the number of levels decompressed. POUR was defined as documented straight catheterization yielding >400 mL. We compared patient demographic, surgical, anesthetic, and postoperative characteristics. A bivariant analysis and backward multivariable stepwise logistic regression analysis ( P -value < 0.200) were performed. Significance was set to P < 0.05. Of the 899 patients identified, 51 met the criteria for POUR and were matched to 153 patients. No notable differences were observed between groups based on demographic or surgical characteristics. On bivariant analysis, patients who developed POUR were more likely to have been given succinylcholine (13.7% vs. 3.92%, P = 0.020) as an induction agent. The independent predictors of POUR identified by multivariable analysis included the use of succinylcholine {odds ratio (OR), 4.37 (confidence interval [CI], 1.26 to 16.46), P = 0.022} and reduced postoperative activity (OR, 0.99 [CI, 0.993 to 0.999], P = 0.049). Factors protective against POUR included using sugammadex as a reversal agent (OR, 0.38 [CI, 0.17 to 0.82], P = 0.017). The stepwise regression did not identify an anterior surgical approach as a notable predictor of POUR. We demonstrate that sugammadex for anesthesia reversal was protective against POUR while succinylcholine and reduced postoperative activity were associated with the development of POUR. In addition, we found no difference between the anterior or posterior approach to spinal fusion in the development of POUR.

Exploiting a rodent cell block for intrinsic resistance to HIV-1 gene expression in human T cells.

Unlike humans, mice are unable to support HIV-1 infection. This is due, in part, to a constellation of defined minor, species-specific differences in conserved host proteins needed for viral gene expression. Here, we used precision CRISPR/Cas9 gene editing to engineer a "mousified" version of one such host protein, cyclin T1 (CCNT1), in human T cells. CCNT1 is essential for efficient HIV-1 transcription, making it an intriguing target for gene-based inactivation of virus replication. We show that isogenic cell lines engineered to encode CCNT1 bearing a single mouse-informed amino acid change (tyrosine in place of cysteine at position 261) exhibit potent, durable, and broad-spectrum resistance to HIV-1 and other pathogenic lentiviruses, and with no discernible impact on host cell biology. These results provide proof of concept for targeting CCNT1 in the context of one or more functional HIV-1 cure strategies.

CDK8 inhibitors antagonize HIV-1 reactivation and promote provirus latency in T cells.

Latent HIV-1 provirus represents the barrier toward a cure for infection and is dependent upon the host RNA Polymerase (Pol) II machinery for reemergence. Here, we find that inhibitors of the RNA Pol II mediator kinases CDK8/19, Senexin A and BRD6989, inhibit induction of HIV-1 expression in response to latency-reversing agents and T cell signaling agonists. These inhibitors were found to impair recruitment of RNA Pol II to the HIV-1 LTR. Furthermore, HIV-1 expression in response to several latency reversal agents was impaired upon disruption of CDK8 by shRNA or gene knockout. However, the effects of CDK8 depletion did not entirely mimic CDK8/19 kinase inhibition suggesting that the mediator kinases are not functionally redundant. Additionally, treatment of CD4+ peripheral blood mononuclear cells isolated from people living with HIV-1 and who are receiving antiretroviral therapy with Senexin A inhibited induction of viral replication in response to T cell stimulation by PMA and ionomycin. These observations indicate that the mediator kinases, CDK8 and CDK19, play a significant role for regulation of HIV-1 transcription and that small molecule inhibitors of these enzymes may contribute to therapies designed to promote deep latency involving the durable suppression of provirus expression. IMPORTANCE A cure for HIV-1 infection will require novel therapies that can force elimination of cells that contain copies of the virus genome inserted into the cell chromosome, but which is shut off, or silenced. These are known as latently-infected cells, which represent the main reason why current treatment for HIV/AIDS cannot cure the infection because the virus in these cells is unaffected by current drugs. Our results indicate that chemical inhibitors of Cdk8 also inhibit the expression of latent HIV provirus. Cdk8 is an important enzyme that regulates the expression of genes in response to signals to which cells need to respond and which is produced by a gene that is frequently mutated in cancers. Our observations indicate that Cdk8 inhibitors may be employed in novel therapies to prevent expression from latent provirus, which might eventually enable infected individuals to cease treatment with antiretroviral drugs.

Effect of Polyamidoamine-Dendrimer Nanoparticles Combined with Human Umbilical Vein Endothelial Cell Microenvironment on the Growth and Immune Infiltration of Nasopharyngeal Carcinoma Cell Line CNE-1

In tumor immunotherapy, Treg cells are immune suppressor cells that are difficult to completely eliminate. To address this issue, a nano-delivery system needs to be designed that includes chemotherapeutic agents and multidrug resistance reversal agents to achieve a cascade of immune chemotherapy enhancement. In this study, polyamidoamine-dendrimer (PAMAM) was utilized as the raw material to prepare a dual-sensitive nano-carrier that is both pH and reduction responsive, and loaded with the chemotherapeutic drug doxorubicin (DOX) and the multidrug resistance reversal agent, elacridar (ELC), to generate YPAMAM nanoparticles. Physicochemical property analysis was performed, and the effect of the nanoparticles on extracellular anti-angiogenesis was examined using human umbilical vein endothelial cells (HUVEC). A culture microenvironment was established using human nasopharyngeal carcinoma cells (CNE-1) and YPAMAM-HUVEC, which was rolled into three groups: 100% CNE-1 supernatant (group A), 50% HUVEC-YPAMAM (5:1) supernatant+50% CNE-1 supernatant (group B), and 100% HUVEC-YPAMAM (5:1) supernatant (group C). The effect of each group on the growth and immune infiltration of CNE-1 cells was analyzed. Fourier-transform infrared spectroscopy (FTIR) showed that the nano-carrier was successfully synthesized, and the particle size of the nanoparticles with various DOX/ELC ratios ranged between 10–20 nm. The prepared nanoparticles exhibited high encapsulation efficiency and simultaneous release of both drugs, with a clear reduction and pH sensitivity. Furthermore, nanoparticles applied to HUVEC could promote vascular rupture, and fluorescence staining showed that the microenvironment could reduce VEGF level and inhibit tumor metastasis. The CNE-1 cell adhesion rate and proliferation rate of groups B and C were dramatically inferior to those of group A (P &lt;0.01). Comparison of the various tumor tissue extract groups indicated that the established microenvironment could inhibit the infiltration of CNE-1 cells in tissue, thereby demonstrating that the constructed microenvironment can improve the immunosuppressive effect of tumors.

Andexanet Alfa Should Be Used to Reverse Factor Xa Inhibitors in the Setting of Life-Threatening Bleeding.

Andexanet alfa was approved by the Food and Drug Administration for reversal of factor Xa inhibitors, apixaban and rivaroxaban, in the setting of acute major bleeding. 1 Connolly S.J. Crowther M. Eikelboom J.W. et al. Full study report of andexanet alfa for bleeding associated with factor Xa inhibitors. N Engl J Med. 2019; 380: 1326-1335 Crossref PubMed Scopus (454) Google Scholar ,2 Siegal D.M. Curnutte J.T. Connolly S.J. et al. Andexanet alfa for the reversal of factor Xa inhibitor activity. N Engl J Med. 2015; 373: 2413-2424 Crossref PubMed Scopus (786) Google Scholar Andexanet alfa and prothrombin complex concentrate have been studied for factor Xa inhibitor reversal. The andexanet alfa is the preferred reversal agent for factor Xa inhibitor bleeds because of its targeted pharmacology for reversal, hemostatic efficacy, mortality outcomes, and its endorsement by numerous guidelines as the preferred agent.