The Relationship between the Measured Blood Concentration of Rocuronium in Stable Muscle Relaxation with a Closed-Loop Control and the Estimated Blood Concentration from a Pharmacokinetic Simulation.

We developed a system to adjust the rate of a continuous rocuronium (Rb) infusion to achieve 3 ≤ %T1 ≤ 10 with a closed-loop control. Samples were collected from 15 patients, and Rb blood concentrations were measured at the following time points: (1) when %T1 recovered to 3% or more after the initial Rb infusion; (2) when %T1 stabilized within the target range; (3) at the cessation of the Rb infusion; (4) 5 min after the sugammadex administration. The predicted Rb blood concentration at each time point was calculated and recorded using the pharmacokinetic parameters of Wierda et al. At time points (1), (2), and (3), the predicted blood concentrations were in good agreement with the measured values, but after the administration of sugammadex, the blood concentrations were higher than the predicted values because the Rb distributed in the tissues migrated into the blood. From the above, it was confirmed that the predicted blood concentration of Rb can be a good indicator for the automatic Rb administration control.

Anesthesia Management via an Automated Control System for Propofol, Remifentanil, and Rocuronium Compared to Management by Anesthesiologists: An Investigator-Initiated Study.

BACKGROUND: We previously developed an automated total intravenous anesthesia control system that uses new closed-loop system algorithms to administer propofol, remifentanil, and rocuronium based on the bispectral index and train-of-four data. We recently improved this automated control system by adding a safety mechanism and using a modified monitoring device. METHODS: Patients scheduled for elective surgery were randomly assigned to closed-loop feedback control (automatic group) or the manual administration of propofol, remifentanil, and rocuronium (manual group). The proportion of time during which the proper management of three-agent anesthesia was maintained during surgery was determined as the primary endpoint. RESULTS: The proportion of time during which the three components of sedation, analgesia, and muscle relaxation were adequately controlled was 87.21 ± 12.79% in the automatic group, which was non-inferior to the proportion of 65.19 ± 20.16% in the manual group (p < 0.001). Adverse events during the operative or postoperative observation periods were significantly less frequent in the automatic group (54 patients, 90.0%) than in the manual group (60 patients, 100.0%; p = 0.027). CONCLUSION: Our three-agent automated control system, which features an improved muscle relaxation monitor and safety mechanism added to the basic control algorithms, maintained sedation, analgesia, and muscle relaxation appropriately in a manner non-inferior to anesthesiologists without compromising safety.

Theoretical and evidence-based infection control during general anesthesia in the COVID-19 pandemic.

With the outbreak of COVID-19, attention has focused on measures to prevent droplet infection. Operating rooms, where we anesthesiologists mainly work, are equipped with various theories and techniques for performing surgical procedures and general anesthesia on patients with various infectious diseases, whether airborne, droplet, or contact infection, and are an environment where surgical procedures and general anesthesia can be safely performed on patients with compromised immune functions. Here, we describe the anesthesia management standards assuming COVID-19 from the viewpoint of medical safety, as well as the structure for supplying clean air in the operating room and the structure of a negative-pressure operating room.

Refractory immune thrombocytopenic purpura associated with IgM monoclonal gammopathy of undetermined significance: Successful treatment with tirabrutinib plus conventional therapies.

When immune thrombocytopenia (ITP) is secondary to malignant diseases, chemotherapy is expected to improve the platelet count (PC) as well. Herein, we report a case of a 72-year-old man with ITP refractory to standard therapies. IgM monoclonal gammopathy of undetermined significance (MGUS) was determined as an underlying disease. After bendamustine and rituximab (BR) therapy was found inadequately effective, tirabrutinib, a novel Bruton's tyrosine kinase inhibitor, was initiated, and the PC normalised subsequently. Surveillance of underlying diseases with which effective therapies are available may help manage refractory ITP, and IgM-MGUS is potentially a targetable underlying disease with this newly available drug.

Synthesis of Pyridine-SF4-Isoxazolines Using the Functionality of trans-Tetrafluoro-λ6-sulfanyl Rodlike Linkers.

The tetrafluoro-λ6-sulfanyl (SF4) moiety has been relatively undeveloped since its discovery in the 1970s. In this study, we synthesized pyridine-SF4-isoxazolines, in which the two heterocycles are connected by a rodlike trans-SF4 linker, via the regioselective 1,3-dipolar cycloaddition of pyridine-SF4-alkynes and nitrones in the presence of triethylamine. SF4 linkers are a viable alternative to para-substituted benzenes, alkynes, and bicyclo[1.1.1]pentyl derivatives in drug design, and pyridine-SF4-isoxazolines have potential applications in drug development.

Regioselective Synthesis of Pyridine-SF4-Methyl Ketones via Hydration of Pyridine-SF4-Alkynes.

Herein, we report the metal-free hydration of pyridine-SF4-alkynes, under acidic conditions and with reaction durations ranging from 5 min to 10 h at room temperature, to synthesize pyridine-SF4-methyl ketones in yields of 59-93%. Further, we demonstrate the synthetic applications of the synthesized pyridine-SF4-methyl ketones, such as chlorination, NaBH4 reduction, Baeyer-Villiger oxidation, and the generation of enol-triflates. These compounds hold promise as useful building blocks in the syntheses of a wide range of SF4-containing drug candidates.

Ethynyl-SF4-Pyridines: Reagents for SF4-Alkynylation to Carbonyl Compounds.

The trans-tetrafluoro-λ6-sulfanyl (SF4) unit is medicinally attractive because of its high electronegativity, lipophilicity, and unique hypervalent structure. The trans-SF4 unit can characteristically connect two independent molecules linearly. However, there is no example of the use of this unit for medicinal chemistry due to difficulties in synthesis. We report the first synthesis of (ethynyl-trans-tetrafluoro-λ6-sulfanyl)pyridines (t-ethynyl-SF4-pyridines) and their use as versatile reagents for the first direct SF4-alkynylation to carbonyl compounds. The addition reaction of t-ethynyl-SF4-pyridines to the carbonyl group in the presence of MeLi smoothly afforded pyridine-SF4-propargylic tertiary and secondary alcohols in high yields.

Synthesis of an Eccentric Electron-Deficient Fluorinated Motif, Tetrafluoro-λ6-sulfanyl gem-Difluorocyclopropenes.

Fluoro-functionalization is now recognized as a critical strategy in drug discovery; however, the accessible fluoro-functional groups are limited. We herein introduce an eccentric, fully fluorinated motif, trans-tetrafluoro-λ6-sulfanyl gem-difluorocyclopropene 2. This novel motif is highly lipophilic and polarized, enabling a connection of two independent groups via three continuous atoms with a large angle of pseudo cis configuration. The target motif was synthesized via a [2+1] cycloaddition of electron-deficient (hetero)aryl-SF4-alkynes 1 with an electrophilic difluorocarbene source.

Three cases of difficulty in achieving definitive loss of consciousness with remimazolam.

BACKGROUND: Remimazolam is a novel, ultra-short-acting benzodiazepine used for general anesthesia. Because remimazolam is an emerging drug, the tolerance to remimazolam in benzodiazepine-taking patients has been unclear. Also, the efficacy of remimazolam in different races is not fully elucidated so far. CASE PRESENTATION: Here we experienced three cases in which high dose of remimazolam was needed for attempting to achieve appropriate anesthetic depth. Two of the three cases were of preoperatively benzodiazepine-taking patients. The other was a case of a Chinese patient. In all three cases, conversion to general anesthesia with propofol was necessitated. CONCLUSIONS: When signs of inadequate sedative effect of remimazolam are observed in patients of benzodiazepine users or of different races, conversion to another sedative agent such as propofol should be considered.

Safety and efficacy of an automated anesthesia delivery system for total intravenous anesthesia with propofol, remifentanil, and rocuronium: a non-inferiority randomized controlled trial versus manually controlled anesthesia.

PURPOSE: We have developed an automated anesthesia control system that uses biological information to provide closed-loop control of drug administration for total intravenous anesthesia with propofol, remifentanil, and rocuronium. In this study, we investigated whether the control of sedatives, analgesics, and muscle relaxants delivered by this system is non-inferior to that delivered by anesthesiologists. METHODS: During anesthesia management by our automated administration control system and by anesthesiologists, the concentration of each drug at the site of effect (calculated from drug administration history) and biometric information (bispectral index, blood pressure, pulse rate, and single contraction ratio %T1) were tabulated during the period from the start to end of surgery. The primary efficacy endpoint was the ratio of adequate anesthesia time, in which all three factors of sedation, analgesia, and muscle relaxation were maintained within the target range, to the period from the start to end of surgery under total intravenous anesthesia. RESULTS: Percentage of time under appropriate anesthesia was 73.24 ± 17.24 in the automatic group (n = 28) and 59.94 ± 29.06 in the manual group (n = 28). The lower limit of the 97.5% one-sided confidence interval for the difference between the two group means was 0.51%, indicating the non-inferiority of the automatic group to the manual group (p = 0.002). The incidence of adverse events did not differ significantly between the groups. CONCLUSION: The clinical use of our automated anesthesia control system should allow for the maintenance of adequate anesthesia by adjusting the doses of intravenous anesthetics in the same way as anesthesiologists do.

Acute Pulmonary Graft-Versus-Host Disease in a Patient with Adult T-cell Leukemia-Lymphoma Diagnosed by a Cryobiopsy.

A 51-year-old woman with adult T-cell leukemia-lymphoma was hospitalized in order to undergo allogeneic hematopoietic stem-cell transplantation. On day 29 after transplantation, she began to experience hypoxia upon exertion. Chest computed tomography revealed centrilobular granular shadows, and pulmonary function tests revealed a remarkable obstructive ventilatory impairment compared to before transplantation. A histopathological analysis following a transbronchial lung cryobiopsy revealed acute graft-versus-host disease (GVHD). We herein report a rare case of histopathologically diagnosed acute pulmonary GVHD with spontaneous remission.

ß-Selective Glycosylation Using Axial-Rich and 2-O-Rhamnosylated Glucosyl Donors Controlled by the Protecting Pattern of the Second Sugar.

Herein, we describe two counterexamples of the previously reported ß/α-selectivity of 96/4 for glycosylation using ethyl 2-O-[2,3,4-tris-O-tert-butyldimethylsilyl (TBS)-α-L-rhamnopyranosyl]-3,4,6-tris-O-TBS-thio-ß-D-glucopyranoside as the glycosyl donor. Furthermore, we investigated the effects of protecting group on the rhamnose moieties in the glycosylation with cholestanol and revealed that ß-selectivity originated from the two TBS groups at the 3-O and 4-O positions of rhamnose. In contrast, the TBS group at the 2-O position of rhamnose hampered the ß-selectivity. Finally, the ß/α-selectivity during the glycosylation was enhanced to ≥99/1. The results obtained herein suggest that the protecting groups on the sugar connected to the 2-O of a glycosyl donor with axial-rich conformation can control the stereoselectivity of glycosylation.

Long-term prognosis of preserved useful hearing after surgery in patients with vestibular schwannoma: a study of 91 cases.

BACKGROUND: In patients with a vestibular schwannoma, some studies have reported that useful hearing preserved initially after surgery deteriorates gradually in the long term. Studies with more patients are needed to clarify the maintenance rate of postoperative hearing function and to identify prognostic of hearing function. METHOD: Ninety-one patients (mean age, 39.5 years; mean tumor size, 18.9 mm) with preserved useful hearing immediately after surgery were retrospectively analyzed. The useful hearing was defined as the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) classes A and B. Hearing tests, including auditory brainstem responses (ABR) and distortion product otoacoustic emissions (DPOAE), were evaluated preoperatively, immediately after surgery, and at outpatient follow-up. RESULTS: At the final follow-up (mean, 63.0 months), the useful hearing was maintained in 79 patients (87%), and the hearing class remained unchanged during the follow-up period in 40 patients (44%). Significant predictors of useful hearing maintenance were AAO-HNS class A immediately after surgery, improvement of ABR, and the absence of postoperative DPOAE deterioration. Postoperative DPOAE deterioration correlated with hearing class deterioration. CONCLUSIONS: Despite hearing being preserved in vestibular schwannoma patients immediately after surgery, Thirteen percent lost their useful hearing during the long follow-up period, and hearing class worsened in 55% of the patients. This study, which analyzed one of the largest series of vestibular schwannoma patients, demonstrated that retrocochlear condition is a key factor for useful hearing maintenance. In patients with vestibular schwannoma who have preserved hearing function, regular postoperative monitoring of hearing function is as important as regular MRI.

Variations in radioactive cesium accumulation in wheat germplasm from fields affected by the 2011 Fukushima nuclear power plant accident.

Decreasing the transfer of radioactive cesium (RCs) from soil to crops has been important since the deposition of RCs in agricultural soil owing to the Fukushima nuclear power plant accident of 2011. We investigated the genotypic variation in RCs accumulation in 234 and 198 hexaploid wheat (Triticum spp.) varieties in an affected field in 2012 and 2013, respectively. The effects of soil exchangeable potassium (ExK) content to RCs accumulation in wheat varieties were also evaluated. A test field showed fourfold differences in soil ExK contents based on location, and the wheat varieties grown in areas with lower soil ExK contents tended to have higher grain RCs concentrations. RCs concentrations of shoots, when corrected by the soil ExK content, were positively significantly correlated between years, and RCs concentrations of shoots were significantly correlated with the grain RCs concentration corrected by the soil ExK content. These results indicated that there were genotypic variations in RCs accumulation. The grain to shoot ratio of RCs also showed significant genotypic variation. Wheat varieties with low RCs accumulations were identified. They could contribute to the research and breeding of low RCs accumulating wheat and to agricultural production in the area affected by RCs deposition.

The Pringle maneuver reduces the infusion rate of rocuronium required to maintain surgical muscle relaxation during hepatectomy.

INTRODUCTION: We investigated the continuous infusion rates of rocuronium necessary to obtain the surgical muscle relaxation before, during, and after the Pringle maneuver on patients who underwent hepatectomy. METHODS: Fifteen patients were induced by total intravenous anesthesia with propofol. After obtaining the calibration of acceleromyography, the patient was intubated with rocuronium 0.6 mg/kg. Fifteen minutes after initial rocuronium injection, the continuous infusion was started at 7.5 µg/kg/min. The infusion rate was adjusted every 15 min so that the first twitch height (% T1) might become from 3 to 10% of control. The infusion rates at the time when the state of surgical muscle relaxation was achieved for more than 15 min were recorded before, during and after the Pringle maneuver. The 25% recovery time was measured after discontinuing the continuous infusion. RESULTS: The infusion rate of rocuronium before, during, and after the Pringle maneuver was 7.2 ± 1.8, 4.2 ± 1.4, and 4.7 ± 1.5 µg/kg/min (mean ± SD), respectively. The rocuronium infusion rate during the Pringle maneuver was decreased about 40% compared to that before this maneuver, and that after completion of the Pringle maneuver was not recovered to that before the Pringle maneuver. The 25% recovery time was 20 ± 7 min. CONCLUSION: In case of continuous administration of rocuronium during surgery performing the Pringle maneuver, it was considered necessary to regulate the administration of rocuronium using muscle relaxant monitoring in order to deal with the decrease in muscle relaxant requirement by the Pringle maneuver.