Evaluation of the accuracy of ChatGPT's responses to and references for clinical questions in physical therapy.

[Purpose] This study evaluated the accuracy of ChatGPT's responses to and references for five clinical questions in physical therapy based on the Physical Therapy Guidelines and assessed this language model's potential as a tool for supporting clinical decision-making in the rehabilitation field. [Participants and Methods] Five clinical questions from the "Stroke", "Musculoskeletal disorders", and "Internal disorders" sections of the Physical Therapy Guidelines, released by the Japanese Society of Physical Therapy, were presented to ChatGPT. ChatGPT was instructed to provide responses in Japanese accompanied by references such as PubMed IDs or digital object identifiers. The accuracy of the generated content and references was evaluated by two assessors with expertise in their respective sections by using a 4-point scale, and comments were provided for point deductions. The inter-rater agreement was evaluated using weighted kappa coefficients. [Results] ChatGPT demonstrated adequate accuracy in generating content for clinical questions in physical therapy. However, the accuracy of the references was poor, with a significant number of references being non-existent or misinterpreted. [Conclusion] ChatGPT has limitations in reference selection and reliability. While ChatGPT can offer accurate responses to clinical questions in physical therapy, it should be used with caution because it is not a completely reliable model.

Integrin alpha 2 is associated with tumor progression and postoperative recurrence in non-small cell lung cancer.

BACKGROUND: Integrins are transmembrane proteins that mediate cell adhesion to extracellular matrix. Whereas expression of integrin alpha 2 is associated with motility, invasiveness and cellular differentiation in various tumors, the role of integrin alpha 2 in lung cancer has not been studied in detail. The aim of this study was to determine whether and how aberrant integrin alpha 2 expression in non-small cell lung cancer leads to different outcomes. METHODS: We measured expression of integrin alpha 2 by quantitative polymerase chain reaction in 100 samples collected from non-small cell lung cancer patients who had undergone surgical resection. We assigned patients to high and low expression groups and analyzed survival. Cellular morphology, adhesion, proliferation, migration and invasion were examined in human lung cancer cell lines. RESULTS: Among 100 cases, 41 were female, with a median age of 71 years. High expression of integrin alpha 2 in non-small cell lung cancer was associated with lower recurrence-free survival (P = 0.004). Overexpression of integrin alpha 2 in cell lines had no effect on cell proliferation or invasion but resulted in increased cell size (1416 µm2 versus 470 µm2 in H522 cells, P < 0.001; 1822 µm2 versus 1029 µm2 in H661 cells, P = 0.02), adhesion (P < 0.001 in H522 and H661 cells) and migration (gap area filled was 71% versus 36% in H522 cells, P < 0.001; 57% versus 26% in H661 cells, P = 0.001). These changes were suppressed by E7820, an inhibitor of integrin alpha 2. CONCLUSIONS: Integrin alpha 2 may play a significant role in lung cancer adhesion and migration, and may lead to a higher risk of recurrence.

Computed Tomography Attenuation Values of the High-Attenuating Crescent Sign Can Discriminate Between Rupture, Impending Rupture, and Non-Rupture of Aortic Aneurysms.

BACKGROUND: Although the high-attenuating crescent (HAC) sign can indicate aortic aneurysm (AA) impending rupture, the relation of its computed tomography (CT) value to the aneurysmal status remains unclear. This study compared the HAC sign CT-attenuation values among rupture, impending rupture, and non-rupture AA cases.Methods and Results:This included 76 patients (mean age: 77.0 years) diagnosed with HAC sign-associated AA between January 2005 and July 2015. The CT-attenuation values of the HAC sign (H) and aortic lumen (A) using region-of-interest methodology were measured and the H/A ratio was calculated. The study classified patients into the rupture group (R-G, n=36), impending rupture group (IR-G, n=16), and non-rupture group (NR-G, n=24); the H and the H/A ratio were compared among them. Additionally, the H and the H/A ratio cut-offs between the IR-G and NR-G groups were evaluated. The H and the H/A ratio were significantly higher in the R-G and IR-G than in the NR-G (both P<0.001); the H/A ratio was significantly higher in the R-G than in the IR-G (P=0.038). The optimal cut-off for H between the IR-G and NR-G was 50.3 Hounsfield units (area under the curve [AUC]=0.875; sensitivity=87.5%; specificity=87.5%), and that for the H/A ratio was 1.3 (AUC=0.909; sensitivity=91.7%; specificity=87.5%). CONCLUSIONS: Among patients with AA, the H and the H/A ratio were significantly higher in cases of rupture and impending rupture than in those of non-rupture.

Preoperative use of pirfenidone and reduced risk of postoperative severe respiratory complications in patients with idiopathic pulmonary fibrosis: Propensity score-matched analysis using a nationwide database in Japan.

BACKGROUND AND OBJECTIVE: Patients with idiopathic pulmonary fibrosis (IPF) often develop postoperative severe respiratory complications such as acute exacerbation. Pirfenidone, an oral anti-fibrotic drug, may reduce the incidence of such complications. However, the preventive effect of pirfenidone on postoperative severe respiratory complications remains unclear. METHODS: We identified patients with IPF who underwent surgery with general anaesthesia from July 2010 to March 2018 using the Diagnosis Procedure Combination database. We compared the occurrence of postoperative severe respiratory complications (receiving mechanical ventilation under endotracheal intubation and/or intravenous infusion of a high-dose corticosteroid and in-hospital death within 30 days after surgery) between patients who did and did not receive preoperative treatment with pirfenidone. Pearson's chi-square test and logistic regression analysis fitted with a generalized estimating equation were conducted in 1:4 propensity score-matched patients. RESULTS: Among 631 patients identified, 19% were treated with pirfenidone before surgery. The 30-day mortality rate was 3.1% and 1.7% in the control patients (n = 510) and pirfenidone-treated patients (n = 121), respectively. In the propensity score-matched population, preoperative treatment with pirfenidone was significantly associated with a lower proportion of postoperative severe respiratory complications (OR: 0.24; 95% CI: 0.07-0.76; p = 0.015). CONCLUSION: In this Japanese nationwide cohort, preoperative treatment with pirfenidone was significantly associated with a lower risk of postoperative severe respiratory complications in patients with IPF. Preoperative pirfenidone may thus be useful in preventing postoperative severe respiratory complications in patients with IPF who are planning to undergo surgery with general anaesthesia.

Integrin α11 in non-small cell lung cancer is associated with tumor progression and postoperative recurrence.

Integrins are transmembrane proteins that mediate cell adhesion to the extracellular matrix. Integrin α11 (ITGA11) is not expressed in normal alveolar epithelial cells and is a known receptor for collagen. While integrin α11ß1 overexpression in the tumor stroma has been associated with tumor growth and metastatic potential of non-small cell lung cancer (NSCLC), little is known about the role of ITGA11 in tumor cells. Thus, we examined the RNA expression of ITGA11 by quantitative RT-PCR in 80 samples collected from NSCLC patients who had undergone surgical resection and analyzed the clinical outcomes. We found that high expression of ITGA11 was associated with lower recurrence-free survival in all NSCLC patients (P = 0.043) and in stage I NSCLC patients (P = 0.049). These results were consistent with in silico analyses of the Cancer Genome Atlas database. We also analyzed cell proliferation, migration and invasion capacity in lung cancer cell lines after overexpression of ITGA11. Overexpression of ITGA11 in lung cancer cell lines had little effect on cell proliferation but resulted in increased migration and invasion capacity. Our findings suggest that ITGA11 plays a significant role in cancer migration and invasion, leading to higher recurrence. ITGA11 expression may be a predictor of poor prognosis in patients with surgically resected NSCLC.

Early Arterial Embolization and Mortality in Mechanically Ventilated Patients With Hemoptysis: A Nationwide Retrospective Cohort Study.

OBJECTIVES: Hemoptysis, a symptom common across various respiratory diseases, can cause airway obstruction leading to a life-threatening condition. Arterial embolization has been used to control bleeding from the lower airways. However, limited studies have evaluated its effects on in-hospital mortality in patients with hemoptysis requiring mechanical ventilation. The objective of this study was to clarify whether early intervention by arterial embolization reduced mortality in mechanically ventilated patients with hemoptysis. DESIGN: Retrospective cohort study from July 2010 to March 2017. SETTING: More than 1,200 acute-care hospitals, comprising approximately 90% of all tertiary-care emergency hospitals in Japan. PATIENTS: The study cohort was patients with pulmonary diseases hospitalized for hemoptysis and mechanically ventilated within 2 days of admission. INTERVENTIONS: We compared patients who had undergone arterial embolization within 3 days of endotracheal intubation (early embolization group) with patients who did not (control group). MEASUREMENTS AND MAIN RESULTS: A total of 12,287 patients with hemoptysis requiring mechanical ventilation were analyzed. After 1:4 propensity score matching, there were 226 and 904 patients in the early embolization and control groups, respectively. The early embolization group was associated with lower 7-day and 30-day mortalities (7-d mortality: 1.3% vs 4.0%; odds ratio, 0.39; 95% CI, 0.16-0.97; p = 0.044 and 30-d mortality: 7.5% vs 16.8%; odds ratio, 0.45; 95% CI, 0.28-0.73; p = 0.001) and shorter duration of mechanical ventilation (median 6 d, interquartile range 4-13 d vs 8 d, interquartile range 4-19 d; p = 0.003) compared with the control group. CONCLUSIONS: Our results show that early intervention by arterial embolization may be effective in reducing 7-day and 30-day mortalities in patients with life-threatening hemoptysis requiring mechanical ventilation.

Multiparametric flow analysis using four-dimensional flow magnetic resonance imaging can detect cerebral hemodynamic impairment in patients with internal carotid artery stenosis.

PURPOSE: MRI-based risk stratification should be established to identify patients with internal carotid artery stenosis (ICS) who require further PET or SPECT evaluation. This study assessed whether multiparametric flow analysis using time-resolved 3D phase-contrast (4D flow) MRI can detect cerebral hemodynamic impairment in patients with ICS. METHODS: This retrospective study analyzed 26 consecutive patients with unilateral ICS (21 men; mean age, 71 years) who underwent 4D flow MRI and acetazolamide-stress brain perfusion SPECT. Collateral flow via the Willis ring was visually evaluated. Temporal mean flow volume rate (Net), pulsatile flow volume (ΔV), and pulsatility index (PI) at the middle cerebral artery were measured. Cerebral vascular reserve (CVR) was calculated from the SPECT dataset. Patients were assigned to the misery perfusion group if the CVR was < 10% and to the nonmisery perfusion group if the CVR was ≥ 10%. Parameters showing a significant difference in both groups were statistically evaluated. RESULTS: Affected side ΔV, ratio of affected to contralateral side Net (rNet), and ratio of affected to contralateral side ΔV were significantly correlated to CVR (p = 0.030, p = 0.010, p = 0.015, respectively). Absence of retrograde flow at the posterior communicating artery was observed in the misery perfusion group (p = 0.020). Combined cut-off values of the affected side ΔV (0.18 ml) and rNet (0.64) showed a sensitivity and specificity of 100% and 77.8%, respectively. CONCLUSION: Multiparametric flow analysis using 4D flow MRI can detect misery perfusion by comprehensively assessing blood flow data, including blood flow volume, pulsation, and collateral flow.

Long-Term Outcomes of Bronchial Artery Embolization for Patients with Non-Mycobacterial Non-Fungal Infection Bronchiectasis.

BACKGROUND: There is no study on the predictive factors of recurrent haemoptysis after bronchial artery embolization (BAE) with the long-term outcomes in patients with bronchiectasis (BE). OBJECTIVES: To evaluate the long-term outcomes of BAE in BE patients without accompanying refractory active infection of mycobacteriosis and aspergillosis with analysis for the predictive factors of recurrent haemoptysis. METHODS: Data of 106 patients with BE who underwent BAE using coils between January 2011 and December 2018 were retrospectively reviewed. The cumulative haemoptysis control rate was estimated using Kaplan-Meier methods with log-rank tests to analyze differences in recurrence-free rate between groups based on technical success and failure, bacterial colonization status, number of BE lesions, and vessels embolized to bronchial arteries (BAs) or BAs + non-bronchial systemic arteries (NBSAs). RESULTS: Bacterial colonization was detected in approximately 60% of patients. Computed tomography showed bronchiectatic lesions with 2.9 ± 1.4 lobes. In the first series of BAE, embolization was performed in the BAs alone and BAs + NBSAs in 65.1 and 34.9% of patients, respectively, with 2.4 ± 1.4 embolized vessels in total. The median follow-up period was 1,000 (7-2,790) days. The cumulative haemoptysis control rates were 91.3, 84.2, 81.5, and 78.9% at 1, 2, 3, and 5 years, respectively. The haemoptysis control rates were higher in the technical success group than in the technical failure group (p = 0.029). CONCLUSIONS: High haemoptysis control rates for long-term periods were obtained by embolization for all visualized abnormal arteries, regardless of the colonization status, number of bronchiectatic lobes, and target vessels, irrespective of NBSAs.

Altered editing level of microRNAs is a potential biomarker in lung adenocarcinoma.

Adenosine-to-inosine (A-to-I) microRNA editing is associated with tumor phenotypes in various cancer types. Recent analyses of The Cancer Genome Atlas (TCGA) dataset have shown several microRNAs that undergo A-to-I editing in human cancers, some of which have been reported to be associated with prognosis. Herein, we examined published small RNA deep sequencing data of 74 cases of lung adenocarcinoma (AD) and the corresponding normal counterpart (NC) specimen in silico in order to identify A-to-I microRNA editing events. Editing levels of miR-379-5p, miR-99a-5p, and miR-497-5p were lower in AD than in NC and, in a large number of cases, the editing level of miR-200b-3p was higher in AD than in NC. Difference in the editing level between AD and NC was largest for miR-99a-5p. Then, we examined the editing level of miR-99a-5p in 50 surgically resected lung adenocarcinoma cases at our institution by a conventional sequence-based method, and its association with clinical outcomes. The editing level of miR-99a-5p was significantly lower in 19 cases of AD (38%) than in corresponding NC. These cases showed a shorter overall survival as assessed using the log-rank test (P = .047). This trend was consistent with previous analyses of TCGA dataset. The altered editing level of microRNAs in lung adenocarcinoma could serve as a potential biomarker.

Glutamate-cysteine ligase catalytic subunit is associated with cisplatin resistance in lung adenocarcinoma.

BACKGROUND: Cisplatin is a key drug for treating lung adenocarcinoma, and its sensitivity to cisplatin is directly related to prognosis. We aimed to reveal the roles of genes related to glutathione synthesis (glutamate-cysteine ligase catalytic subunit, GCLC) and cystine uptake (cystine/glutamate transporter, xCT and CD44v8-10) in cisplatin resistance and prognosis in lung adenocarcinoma. METHODS: We established cell lines stably expressing GCLC, xCT, standard isoform of CD44, and CD44v8-10, and investigated their sensitivities to cisplatin. We also measured mRNA expression levels of these genes in the tumor tissues from 92 lung adenocarcinoma patients. Patients were divided into high-expression (upper quartile, N = 23) and low-expression groups (remaining patients, N = 69). Recurrence-free survival, overall survival (N = 92), and post-recurrence survival (N = 22) were selected as endpoints. RESULTS: Compared with the control green fluorescent protein-expressing cell line (inhibitory concentration 50:6.9 µM), all the stable cell lines were more resistant to cisplatin (12.9 µM, P = 0.025; 13.9 µM, P = 0.028; 26.7 µM, P = 0.001; 17.7 µM, P = 0.008, respectively). In contrast, there was no significant difference in recurrence-free or overall survival between the high- and low-expression groups for any of the genes. However, high expression of GCLC was a risk factor for poorer post-recurrence survival (hazard ratio, 6.26; 95% confidence interval, 1.37-28.7; P = 0.018). CONCLUSION: High expression levels of genes related to glutathione synthesis and cystine uptake promote cisplatin resistance in lung adenocarcinoma cell lines. High expression of GCLC in tumor tissue may be a potential predictor of treatment failure.

Clinical Features and Prognosis of Nontuberculous Mycobacterial Pleuritis.

BACKGROUND: While nontuberculous mycobacterial (NTM) pleuritis rarely complicates pulmonary NTM infection, high mortality has been reported in case reports and small studies. OBJECTIVES: The purpose of this study was to clarify the clinical features and treatment outcomes of pulmonary NTM infection cases accompanied by NTM pleuritis. METHODS: Medical records of 1,044 patients with pulmonary NTM disease were retrospectively reviewed to select patients complicated by NTM-proven pleuritis. We investigated clinical characteristics, pathogens, pleural effusion examinations, radiographic findings, treatments, and clinical course of the NTM pleuritis patients. RESULTS: Among 1,044 cases with pulmonary NTM, NTM pleuritis occurred in 15 cases (1.4%). The mean age was 69 years with a performance status of mostly 2 or better (80.0%), and 6 cases (40.0%) were complicated by pneumothorax. Subpleural cavities were radiologically detected in 11 cases (73.3%), and extrapulmonary air-fluid level was detected in 14 cases (93.3%). Eleven patients were treated with combinations of 2-4 antimycobacterial drugs, including clarithromycin, and 2 patients were treated with isoniazid, rifampicin, and ethambutol. Chest tube drainage was performed in 11 cases, and surgical approach was added in 6 cases. The pleural effusion of 2 patients treated with only antimycobacterial medications gradually deteriorated. Two patients died from NTM pleuritis, and 1 patient died from pneumonitis during a mean of 1.8 years of follow-up. CONCLUSIONS: Comorbid NTM pleuritis was difficult to treat by medical therapy alone and resulted in a poor prognosis. In addition to antimycobacterial agents, chest tube drainage and surgical procedures in the early stages should be considered to treat NTM pleuritis.

Early stage non-small cell lung cancer patients need brain imaging regardless of symptoms.

BACKGROUND: Japanese Lung Cancer Society and ESMO guideline recommends screening for brain metastasis in all patients with non-small cell lung cancer (NSCLC), while NCCN/ACCP guidelines do not recommend screening patients who are asymptomatic and with clinical stage I NSCLC. However, brain metastasis sometimes occurs in early stage NSCLC patients without any neurological symptoms. METHODS: We retrospectively reviewed medical records of 124 patients admitted to the University of Tokyo Hospital with stage IV NSCLC from January 2012 to April 2016. We analyzed clinical stage, the presence of the central nervous system manifestations and the number of brain metastases. RESULTS: Forty-six out of 124 cases had brain metastasis at presentation. The brain metastasis group had larger number of female, never smokers and patients with EGFR mutation compared with extracranial metastasis group. Twenty-one of 35 adenocarcinoma cases with brain metastasis had EGFR mutations. Out of 46 brain metastasis patients, 29 patients (63%) were asymptomatic and patients with EGFR mutations were significantly less likely to have neurological symptoms (4/21 vs. 7/14, p = 0.049). Six out of 46 cases with brain metastasis (13%) were clinical T1-2aN0. In clinical T1-2aN0 cases, only one patient had neurological symptoms at presentation. CONCLUSION: In clinical T1-2aN0 lung cancer patients with brain metastasis, almost all patients were asymptomatic. Patients with EGFR mutations and brain metastasis were likely to be asymptomatic. Regardless of central nervous system symptoms, routine brain imaging seems warranted in all NSCLC patients, especially in areas where patients have a higher frequency of EGFR mutations.

Palladium Nanoparticles Encapsulated in Hollow Titanosilicate Spheres as an Ideal Nanoreactor for One-pot Oxidation.

One-pot reaction involving Pd-catalyzed H2 O2 production from H2 and O2 and Ti-catalyzed successive oxidation with H2 O2 in a single reaction vessel is an alluring strategy for the synthesis of targeted chemicals in terms of sustainability and economic competitiveness. In this study, a yolk-shell nanostructured catalyst, consisting of Pd nanoparticles (NPs) with core diameter ca. 4.0 nm and a porous titanosilicate shell of ca. 15 nm thickness, was fabricated by using an oil-in-water (O/W) microemulsion-based interfacial self-assembly approach. Compared with prototype titanosilicate-supported Pd NP catalysts and core-shell structured analogues, the yolk-shell nanostructured catalyst exhibited superior catalytic efficiency in the one-pot oxidation reaction of sulfides with 83 % H2 O2 utilization efficiency, because of the productive effect of the titanosilicate shell in limiting the diffusion of H2 O2 generated in situ over the encapsulated Pd NPs and the efficient access of the H2 O2 to the neighboring active Ti sites. This study provides promising avenues for the development of multifunctional nanostructured catalysts that are useful for one-pot reactions.

Important role of calcium chloride in preventing carbon monoxide generation during desflurane degradation with alkali hydroxide-free carbon dioxide absorbents.

We investigated whether calcium chloride (CaCl2), a supplementary additive in carbon dioxide (CO2) absorbents, could affect carbon monoxide (CO) production caused by desflurane degradation, using a Japanese alkali-free CO2 absorbent Yabashi Lime®-f (YL-f), its CaCl2-free and 1% CaCl2-added derivatives, and other commercially available alkali-free absorbents with or without CaCl2. The reaction between 1 L of desflurane gas (3-10%) and 20 g of desiccated specimen was performed in an artificial closed-circuit anesthesia system for 3 min at 20 or 40 °C. The CO concentration was measured using a gas chromatograph equipped with a semiconductor sensor detector. The systems were validated by detecting dose-dependent CO production with an alkali hydroxide-containing CO2 absorbent, Sodasorb®. Compared with YL-f, the CaCl2-free derivative caused the production of significantly more CO, while the 1% CaCl2-added derivative caused the production of a comparable amount of CO. These phenomena were confirmed using commercially available absorbents AMSORB® PLUS, an alkali-free absorbent with CaCl2, and LoFloSorb™, an alkali-free absorbent without CaCl2. These results suggest that CaCl2 plays an important role in preventing CO generation caused by desflurane degradation with alkali hydroxide-free CO2 absorbents like YL-f.

Thoracoscopic examination of empyema in a patient with sparganosis mansoni.

A 27-year-old man was admitted to our hospital with right pleural effusion. He had suffered from right chest and back pain and a high fever for one week prior to the admission. He had been treated with clarithromycin without improvement. Since thoracoscopy under local anesthesia revealed purulent effusion, synechiae and fibrous septa in the thoracic cavity, synechiotomy was performed and we started antibiotic treatment with the diagnosis of acute bacterial empyema. At the same time, we also suspected parasitic infection because of massive eosinophilic infiltration in pleural effusion and his dietary history of eating raw frogs. During the course of the disease, he had an infiltration in the right lower lobe and pneumothorax. Finally, we diagnosed him with sparganosis mansoni because his serum as well as pleural effusion was positive for the binding to sparganosis mansoni plerocercoid antigen, without any positive findings in bacteriology. His pleural effusion and lung infiltration were resolved after the administration of a high-dose praziquantel. We report this rare parasitic empyema with findings by thoracoscopic examination.

Recurrence of chronic pulmonary aspergillosis after discontinuation of maintenance treatment by antifungal triazoles.

OBJECTIVE: To assess the prevalence and risk factors of recurrence of chronic pulmonary aspergillosis (CPA) after discontinuation of antifungal triazoles. METHOD: We reviewed the medical records of CPA patients who achieved resolution of clinical and radiographic manifestations and stopped taking antifungal triazoles between June 2006 and June 2012 at Tokyo National Hospital. We evaluated whether there was CPA recurrence within 1 year after treatment cessation and investigated risk factors for relapse. The association of anti-Aspergillus antibody conversion with CPA recurrence was also reviewed. RESULTS: A total of 39 patients were included in this study and there was CPA recurrence in 14 patients. Compared with the Non-recurrence group, the Recurrence group exhibited 1) younger age (p = 0.017), 2) more than one lung lobe affected by CPA more frequently (p = 0.008), 3) longer duration needed to remit manifestations of chest radiograph (p = 0.031), 4) longer antifungal treatment duration (p = 0.042). The present study did not reveal an association between negative conversion of serum anti-Aspergillus antibody and recurrence risk. Multivariate logistic regression analysis revealed that patients with CPA with affected area of more than one lung lobe had increased risk (odds ratio, 10.20; 95% confidence interval, 1.49-69.77; p = 0.018). CONCLUSION: CPA recurrence can be seen in about one-third of cases after discontinuing azole treatment. We should make decisions about treatment duration and follow up depending on the severity of each case, particularly on the expansion of CPA-affected area.

Improvement of limit of detection in primer extension-based multiplexed mutation assay using capillary electrophoresis.

One of the challenges in liquid biopsy for early cancer detection is ascribed to the fact that mutation DNA often represents an extremely small ratio of less than 1% compared to wild-type genes in blood. However, in conventional fragment analysis with capillary electrophoresis (CE), the detectable allele frequency could be about 5%. In this work, we developed an original reagent-based fragment analysis with single base extension (SBE) reactions for cancer-associated mutation assay using a commercially available CE device, and investigated on a possibility of improvement of limit of detection (LOD) for genetic mutation. First, after adjustment of reagent conditions for the SBE reactions, the linear relationship between gene template concentration and fluorescence intensity was obtained from 1 to 100 fmol of target genes. Next, from the results of an experiment to detect mutation EGFR L858R at abundance ratios of mutant type to wild type (100-fmol template) of 0, 1, 5, and 10%, it was shown that the target gene can be detected with LOD of 0.33%. This high sensitivity was realized in part by separating fluorescently labeled substrates into an individual tube for an each-colored SBE reaction. Moreover, mutations EGFR L858R and KRAS G12V were simultaneously detected at sensitivities equivalent to LODs of 0.57 and 0.47%, respectively. These results indicate that < 1% of mutations in multiplex gene mutations can be simultaneously detected, and that possibility suggests that the developed method can be used in clinical practice for detecting cancers.

Prospective Randomized Controlled Trial Comparing Anesthetic Management With Remimazolam Besylate and Flumazenil Versus Propofol During Awake Craniotomy Following an Asleep-awake-asleep Method.

BACKGROUND: Awake craniotomy is performed to resect brain tumors in eloquent brain areas to maximize tumor reduction and minimize neurological damage. Evidence suggests that intraoperative anesthetic management of awake craniotomy with remimazolam is safe. We compared the time to arousal and efficacy of anesthetic management with remimazolam and propofol during awake craniotomy. METHODS: In a single-institution randomized, prospective study, patients who underwent elective awake craniotomy were randomized to receive remimazolam and reversal with flumazenil (group R) or propofol (group P). The primary end point was time to awaken. Secondary end points were time to loss of consciousness during induction of anesthesia, the frequency of intraoperative complications (pain, hypertension, seizures, nausea, vomiting, and delayed arousal), and postoperative nausea and vomiting. Intraoperative task performance was assessed using a numerical rating scale (NRS) score. RESULTS: Fifty-eight patients were recruited, of which 52 (26 in each group) were available for the efficacy analysis. Patients in group R had faster mean (±SD) arousal times than those in the P group (890.8±239.8 vs. 1075.4±317.5 s; P=0.013)and higher and more reliable intraoperative task performance (NRS score 8.81±1.50 vs. 7.69±2.36; P=0.043). There were no significant intraoperative complications. CONCLUSIONS: Compared with propofol, remimazolam was associated with more rapid loss of consciousness and, after administration of flumazenil, with faster arousal times and improved intraoperative task performance.