Can Remimazolam Be a New Sedative Option for Outpatients Undergoing Ambulatory Oral and Maxillofacial Surgery?

PURPOSE: Midazolam is a classic sedative drug. The sedative effect of remimazolam has not been demonstrated in ambulatory oral and maxillofacial surgery (OMS). This study aimed to measure whether remimazolam can achieve the same sedation effects compared with midazolam, but with a faster recovery and fewer adverse reactions in outpatients undergoing ambulatory OMS. MATERIALS AND METHODS: This was a prospective, randomized, controlled, single-center study of 40 patients who underwent ambulatory OMS at Peking University Hospital of Stomatology, Beijing, China, between April 2021 and June 2021. The patients were randomly divided into a midazolam group (Group M) and a remimazolam group (Group R). The success rate of sedation, which was defined as completion of the operation with no rescue sedative medication, was the primary outcome. In this study, bispectral index and modified observer's assessment of alertness/sedation value, intraoperative adverse events, time to discharge, and the number of additional doses of sedative were compared. Descriptive, comparative analyses were conducted. RESULTS: Forty patients were eligible for this study, and the final sample size was 40 (including 25 males, average age was 29). The success rate of sedation in Group R was statistically significantly higher than that in Group M (Group R vs Group M: 95% [19/20] vs 70% [14/20], P = .037, 95% confidence interval [CI]: 0.681 to 0.913). The median number of additional doses of the medications per 5 minutes in Group R was lower than that in Group M (0.51 [0.19, 0.71] vs 0.82 [0.51, 1.25], P = .006, 95% CI: 0.013 to 0.583). Group R showed a higher bispectral index number (93.9 ± 4.6 vs 86.6 ± 7.2, P = .001, 95% CI: 3.451 to 11.149) at the end of the surgery and a higher modified observer's assessment of alertness/sedation score (4.70 ± 0.47 vs 4.05 ± 0.68, P = .001, 95% CI: 0.273 to 1.027) after 5 minutes at the recovery room compared with Group M. CONCLUSIONS: The success rate of remimazolam is higher than that of midazolam. The use of remimazolam is effective for sedation of patients undergoing ambulatory OMS.

Preparation of Poly(thiol-urethane) Covalent Adaptable Networks Based on Multiple-Types Dynamic Motifs.

To solve the issue of polymeric materials recycling, developing intrinsic self-healing materials containing dynamic bonds has attracted many researchers' highly concerning. However, the tradeoff between their mechanical strength and stretchability always does not avoid. Herein, to surmount the above tradeoff, metal-ligand (Cu2+ -S) interactions are introduced into the cross-linking polythiourethane covalent adaptable networks (PTU CANs) with three kinds of dynamic motifs (thiourethane, disulfide, and hydrogen bonds). When the molar ratio of Cu2+ to S is 6.37%, the break strength (9.41 ± 0.34 MPa) and Young's modulus (26.02 ± 0.55 MPa) of the metal-ligand coordination complex PTU (Cu2+ -PTU-3) dramatically increase, whereas the peak strain almost does not decline (454.44 ± 3.95%). To conduct the repairing, Cu2+ -PTU-3 is further confirmed excellent repairing capability. Therefore, these new PTU CANs have significant potential for the new self-healing materials.

Tough physically crosslinked poly(vinyl alcohol)-based hydrogels loaded with collagen type I to promote bone regeneration in vitro and in vivo.

Poly(vinyl alcohol) (PVA) hydrogels exhibit great potential as ideal biomaterials for tissue engineering, owing to their non-toxicity, high water content, and strong biocompatibility. However, limited mechanical strength and low bioactivity have constrained their application in bone tissue engineering. In this study, we have developed a tough PVA-based hydrogel using a facile physical crosslinking method, comprising of PVA, tannic acid (TA), and hydroxyapatite (HA). Systematic experiments were conducted to examine the physicochemical properties of PVA/HA/TA hydrogels, including their compositions, microstructures, and mechanical and rheological properties. The results demonstrated that the PVA/HA/TA hydrogels possessed the porous microstructures and excellent mechanical properties. Furthermore, collagen type I (ColI) was used to further improve the biocompatibility and bioactivity of PVA/HA/TA hydrogels. In vitro experiments revealed that PVA/HA/TA/COL hydrogel could offer a suitable microenvironment for the growth of MC3T3-E1 cells and promote their osteogenic differentiation. Meanwhile, the PVA/HA/TA/COL hydrogel demonstrated the ability to promote bone regeneration and osteointegration in a rat femoral defect model. This study provides a potential strategy for the use of PVA-based hydrogels in bone tissue engineering.

Efficacy of ultrasound guided superior laryngeal nerve block on sedation for delayed extubation in maxillofacial surgery with free flap reconstruction.

OBJECTIVE: Superior laryngeal nerve block (SLNB) is a regional anesthesia technique for addressing airway response. However, SLNB on the efficacy of sedation in patients with delayed extubation is unknown, particularly for maxillofacial surgery (MS). The aim of the study was to assess whether ultrasound guided (UG) SLNB reduces the incidence of moderate to severe cough for delayed extubation in MS with free flap reconstruction. METHODS: 60 patients were randomly assigned to the GEA group (control group) and the SLNB group (UG-SLNB postoperatively, study group). During the initial two postoperative hours, the incidence of moderate and severe cough, agitation, and the number of patients requiring rescue propofol and flurbiprofen were recorded. Additionally, the time spent under the target level of sedation, postoperative hemodynamics, and the total does of propofol during the postoperative 24 h were recorded. RESULTS: The data showed the SLNB group had a significantly lower incidence of moderate to severe cough and agitation (p < 0.05), and a longer sedation time (p < 0.05). The number of patients required rescue propofol and flurbiprofen, as well as the hemodynamic changes, were significantly different between the two groups (p < 0.05). CONCLUSION: The use of UG-SLNB is associated with reduced incidence of postoperative cough. Moreover, SLNB can enhance the efficacy of postoperative sedation with need of fewer agents postoperatively. CLINICAL TRIAL REGISTRATION: ChiCTR2000039982.

Fabrication and characterization of porous, degradable, biocompatible poly(vinyl alcohol)/tannic acid/gelatin/hyaluronic acid hydrogels with good mechanical properties for cartilage tissue engineering.

At present, articular cartilage repair and regeneration remain still one of the most concerned problems due to its poor self-healing capacity. Among the tissue engineering materials, hydrogel is considered an ideal candidate due to its similarity to extracellular matrices. Despite the good biocompatibility of gelatin and hyaluronic acid hydrogels, they are still limited to serve as tissue engineering materials by fast degradation rate and poor mechanical performances. In order to solve these problems, novel polyvinyl alcohol/tannic acid/gelatin/hyaluronic acid (PTGH) hydrogels are prepared by a facile physical crosslinked method. The PTGH hydrogels exhibit a high moisture content (85%) and porosity (87%). Meanwhile, the porous microstructures and mechanical properties (compressive strength: 0.85-2.59 MPa; compressive modulus: 57.88-124.27 kPa) can be controlled by adjusting the mass ratio of PT/GH. In vitro degradation analysis shows that the PTGH hydrogels can be degraded gradually in PBS solution with the presence of lysozyme. For this gel system, based on the hydrogen bonds among molecules, it improved the mechanical properties of gelatin and hyaluronic acid hydrogels. With the degradation of PTGH hydrogels, the release of gelatin and hyaluronic acid can have a continuous effort for the cartilage tissue regeneration and repair. In addition, in vitro cell culture results show that the PTGH hydrogels have no negative effects on chondrocytes growth and proliferation. In all, the PTGH hydrogels exhibit potential applications for articular cartilage tissue repair and regeneration.

Six new metal-organic frameworks based on polycarboxylate acids and V-shaped imidazole-based synthon: syntheses, crystal structures, and properties.

Solvothermal reactions of 4,4'-bis(imidazol-1-yl)diphenyl ether (BIDPE) with deprotonated 5-hydroxy-isophthalic acid (5-OH-H(2)bdc), and benzene-1,3,5-tricarboxylic acid (H(3)btc) in the presence of cadmium(II), zinc(II), cobalt(II), nickel(II), and manganese(II) salts in H(2)O or H(2)O/DMF produced six new complexes, namely, [Cd(BIDPE)(5-OH-bdc)·H(2)O](n) (1), [Co(BIDPE)(5-OH-bdc)·H(2)O](n) (2), [Zn(3)(BIDPE)(3)(5-OH-bdc)(3)·4H(2)O](n) (3), [Ni(BIDPE)(2)(5-OH-bdc)(H(2)O)·3H(2)O](n) (4), {[Mn(2)(BIDPE)(2)(5-OH-bdc)(2)](n) (5), and [Ni(BIDPE)(2)(Hbtc)(H(2)O)](n) (6). These complexes were characterized by elemental analysis, IR spectroscopy, and X-ray single-crystal diffraction. Compounds 1 and 2 reveal the same two-dimensional (2D) sheets with a 32-membered [(Cd/Co)(2)(BIDPE)(2)] metallocyclic ring constructed from BIDPE and 5-OH-H(2)bdc with Cd or Co salts. For compound 3, six identical 2D sheets are polycatenated in parallel to form a rare 2D → 2D framework; it displays ferroelectric behavior with a remnant electric polarization (P(r)) of 0.033 µC/cm(2) and an electric coercive field (E(c)) of 11.15 kV/cm. In compounds 4 and 6, only one carboxyl group coordinated to the Ni atom from 5-OH-H(2)bdc or H(3)btc. Compound 5 exists as binuclear Mn clusters, which are linked by BIDPE and 5-OH-H(2)bdc to generate a 2D sheet and displays weak antiferromagnetic character. In addition, the thermal stabilities and photochemical properties of these new complexes have been studied.

Mediation analysis for count and zero-inflated count data without sequential ignorability and its application in dental studies.

Mediation analysis seeks to understand the mechanism by which a treatment affects an outcome. Count or zero-inflated count outcomes are common in many studies in which mediation analysis is of interest. For example, in dental studies, outcomes such as the number of decayed, missing and filled teeth are typically zero inflated. Existing mediation analysis approaches for count data often assume sequential ignorability of the mediator. This is often not plausible because the mediator is not randomized so unmeasured confounders are associated with the mediator and the outcome. We develop causal methods based on instrumental variable approaches for mediation analysis for count data possibly with many 0s that do not require the assumption of sequential ignorability. We first define the direct and indirect effect ratios for those data, and then we propose estimating equations and use empirical likelihood to estimate the direct and indirect effects consistently. A sensitivity analysis is proposed for violations of the instrumental variables exclusion restriction assumption. Simulation studies demonstrate that our method works well for different types of outcome under various settings. Our method is applied to a randomized dental caries prevention trial and a study of the effect of a massive flood in Bangladesh on children's diarrhoea.

Mediation analysis for count and zero-inflated count data.

Different conventional and causal approaches have been proposed for mediation analysis to better understand the mechanism of a treatment. Count and zero-inflated count data occur in biomedicine, economics, and social sciences. This paper considers mediation analysis for count and zero-inflated count data under the potential outcome framework with nonlinear models. When there are post-treatment confounders which are independent of, or affected by, the treatment, we first define the direct, indirect, and total effects of our interest and then discuss various conditions under which the effects of interest can be identified. Proofs are provided for the sensitivity analysis proposed in the paper. Simulation studies show that the methods work well. We apply the methods to the Detroit Dental Health Project's Motivational Interviewing DVD trial for the direct and indirect effects of motivational interviewing on count and zero-inflated count dental caries outcomes.

Dual-drug loaded nanoformulation with a galactosamine homing moiety for liver-targeted anticancer therapy.

Drug resistance and unfavorable pharmacokinetics are the major obstacles for conventional anticancer drugs. A combination of different anticancer drugs into one formulation is a common strategy to alleviate the side effects of individual drugs in clinical practice. Platinum anticancer drugs are the typical defective therapeutic agents for cancer chemotherapy and have poor selectivity for tumor cells. In this study, a nanosystem composed of poly(lactic-co-glycolic acid) (PLGA), Pt(IV) prodrug (PPD) and α-tocopheryl succinate (α-TOS) was designed to overcome these defects. The Pt(IV) prodrug, c,c,t-[Pt(NH3)2Cl2(O2CC(CH3)3)2], was prepared by the reaction of oxoplatin with trimethylacetic anhydride and its structure was characterized by X-ray crystallography. The PPD and α-TOS self-assembled with PLGA, forming a dual-drug loaded nanoparticle (DDNP). The surface of the DDNP was decorated with galactosamine (G), giving rise to a G-DDNP that can actively target the liver cancer cells through the overexpressed asialoglycoprotein receptors. The DDNPs and G-DDNPs were characterized by SEM, TEM, and DLS. They are spherical in shape with required polydispersity and suitable mean size (ca. 150 nm). The in vitro cytotoxicity of DDNPs and G-DDNPs was tested against the human SMMC-7721 liver cancer cell line. G-DDNPs are more potent than the corresponding free drugs and untargeted DDNP, showing that some synergistic and tumor-specific effects are achieved by this strategy. The results demonstrate that dual-drug loaded nanoformulations with tumor-targeting function could be effective anticancer agents for conquering the shortcomings related to single-drug chemotherapy.

An H2O2-responsive nanocarrier for dual-release of platinum anticancer drugs and O2: controlled release and enhanced cytotoxicity against cisplatin resistant cancer cells.

Synergistic release of platinum anticancer drugs and O2 can be achieved in an H2O2-responsive nanocarrier incorporated with catalase. Such a system combines the advantages of chemotherapy and oxygen therapy and demonstrated improved therapeutic efficacy against cisplatin resistant cell lines which often appear to be in hypoxia.