Coapplication of Lidocaine and the Permanently Charged Sodium Channel Blocker QX-314 Produces a Long-lasting Nociceptive Blockade in Rodents

Binshtok, Alexander M.,Gerner, Peter,Oh, Seog Bae,Puopolo, Michelino,Suzuki, Suzuko,Roberson, David P.,Herbert, Teri,Wang, Chi-Fei,Kim, Donghoon,Chung, Gehoon,Mitani, Aya A.,Wang, Ging Kuo,Bean, Bruce American Society of Anesthesiologists, Inc. 2009 Anesthesiology Vol.111 No.1

BACKGROUND:: Nociceptive-selective local anesthesia is produced by entry of the permanently charged lidocaine-derivative QX-314 into nociceptors when coadministered with capsaicin, a transient receptor potential vanilloid 1 (TRPV1) channel agonist. However, the pain evoked by capsaicin before establishment of the QX-314–mediated block would limit clinical utility. Because TRPV1 channels are also activated by lidocaine, the authors tested whether lidocaine can substitute for capsaicin to introduce QX-314 into nociceptors through TRPV1 channels and produce selective analgesia. METHODS:: Lidocaine (0.5% [17.5 mm], 1% [35 mm], and 2% [70 mm]) alone, QX-314 (0.2% [5.8 mm]) alone, and a combination of the two were injected subcutaneously and adjacent to the sciatic nerve in rats and mice. Mechanical and thermal responsiveness were measured, as was motor block. RESULTS:: Coapplication of 0.2% QX-314 with lidocaine prolonged the nociceptive block relative to lidocaine alone, an effect attenuated in TRPV1 knockout mice. The 0.2% QX-314 alone had no effect when injected intraplantary or perineurally, and it produced only weak short-lasting inhibition of the cutaneous trunci muscle reflex. Perisciatic nerve injection of lidocaine with QX-314 produced a differential nociceptive block much longer than the transient motor block, lasting 2 h (for 1% lidocaine) to 9 h (2% lidocaine). Triple application of lidocaine, QX-314, and capsaicin further increased the duration of the differential block. CONCLUSIONS:: Coapplication of lidocaine and its quaternary derivative QX-314 produces a long-lasting, predominantly nociceptor-selective block, likely by facilitating QX-314 entry through TRPV1 channels. Delivery of QX-314 into nociceptors by using lidocaine instead of capsaicin produces sustained regional analgesia without nocifensive behavior.

Experimental Investigation on the Force-Crack Quantification Model for HSRC Columns with Flexure-Shear and Shear Failure Modes

Cien-Kuo Chiu,Alexander Ivan Tandri 한국콘크리트학회 2020 International Journal of Concrete Structures and M Vol.14 No.4

A total of six full-scale high strength reinforced concrete (HSRC) columns were tested under axial and cyclic lateral loading. The specified concrete compressive strength was 70 MPa and the specified yield strength was 685 MPa and 785 MPa for the longitudinal and transverse reinforcements, respectively. The main variables considered in the study are the transverse reinforcements ratio and axial load ratio. Although such HSRC columns have gradually transformed in use and scope, the damage assessment method is less understood. The main purpose of this study is to propose a damage assessment model for HSRC columns. An analytical backbone curve model for predicting force-deformation behavior of HSRC columns is described. Column stiffness is also measured from the experiment to obtain stiffness reduction factors that are necessary to calculate member deformation. Based on experiment results, a new limiting value of residual crack width is defined to determine damage level. This study uses specified residual crack width of 0.15 mm, 0.30 mm, and 1.00 mm in the damage assessment model. The new limiting value of residual crack width is also used to determine the performance points of structural members. Finally, a new drift ratio limit of each damage level is also proposed. Experiment results are presented and used to investigate the application of the proposed damage assessment model.

Endoscopic Anterior Lumbar Interbody Fusion: Systematic Review and Meta-Analysis

Brown Nolan J.,Pennington Zach,Kuo Cathleen C.,Lopez Alexander M.,Picton Bryce,Solomon Sean,Nguyen Oanh T.,Yang Chenyi,Tantry Evelyne K.,Shahin Hania,Gendreau Julian,Albano Stephen,Pham Martin H.,Oh M 대한척추외과학회 2023 Asian Spine Journal Vol.17 No.6

Laparoscopic anterior lumbar interbody fusion (L-ALIF), which employs laparoscopic cameras to facilitate a less invasive approach, originally gained traction during the 1990s but has subsequently fallen out of favor. As the envelope for endoscopic approaches continues to be pushed, a recurrence of interest in laparoscopic and/or endoscopic anterior approaches seems possible. Therefore, evaluating the current evidence base in regard to this approach is of much clinical relevance. To this end, a systematic literature search was performed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines using the following keywords: “(laparoscopic OR endoscopic) AND (anterior AND lumbar).” Out of the 441 articles retrieved, 22 were selected for quantitative analysis. The primary outcome of interest was the radiographic fusion rate. The secondary outcome was the incidence of perioperative complications. Meta-analysis was performed using RStudio’s “metafor” package. Of the 1,079 included patients (mean age, 41.8±2.9 years), 481 were males (44.6%). The most common indication for L-ALIF surgery was degenerative disk disease (reported by 18 studies, 81.8%). The mean follow-up duration was 18.8±11.2 months (range, 6–43 months). The pooled fusion rate was 78.9% (95% confidence interval [CI], 68.9–90.4). Complications occurred in 19.2% (95% CI, 13.4–27.4) of L-ALIF cases. Additionally, 7.2% (95% CI, 4.6–11.4) of patients required conversion from L-ALIF to open surgery. Although L-ALIF does not appear to be supported by studies available in the literature, it is important to consider the context from which these results have been obtained. Even if these results are taken at face value, the failure of endoscopy to have a role in the ALIF approach does not mean that it should not be incorporated in posterior approaches.

Assessing the performance of ChatGPT in answering questions regarding cirrhosis and hepatocellular carcinoma

Yee Hui Yeo,Jamil S. Samaan,Wee Han Ng,Peng-Sheng Ting,Hirsh Trivedi,Aarshi Vipani,Walid Ayoub,Ju Dong Yang,Omer Liran,Brennan Spiegel,Alexander Kuo 대한간학회 2023 Clinical and Molecular Hepatology(대한간학회지) Vol.29 No.3

Background/Aims: Patients with cirrhosis and hepatocellular carcinoma (HCC) require extensive and personalized care to improve outcomes. ChatGPT (Generative Pre-trained Transformer), a large language model, holds the potential to provide professional yet patient-friendly support. We aimed to examine the accuracy and reproducibility of ChatGPT in answering questions regarding knowledge, management, and emotional support for cirrhosis and HCC. Methods: ChatGPT’s responses to 164 questions were independently graded by two transplant hepatologists and resolved by a third reviewer. The performance of ChatGPT was also assessed using two published questionnaires and 26 questions formulated from the quality measures of cirrhosis management. Finally, its emotional support capacity was tested. Results: We showed that ChatGPT regurgitated extensive knowledge of cirrhosis (79.1% correct) and HCC (74.0% correct), but only small proportions (47.3% in cirrhosis, 41.1% in HCC) were labeled as comprehensive. The performance was better in basic knowledge, lifestyle, and treatment than in the domains of diagnosis and preventive medicine. For the quality measures, the model answered 76.9% of questions correctly but failed to specify decision-making cut-offs and treatment durations. ChatGPT lacked knowledge of regional guidelines variations, such as HCC screening criteria. However, it provided practical and multifaceted advice to patients and caregivers regarding the next steps and adjusting to a new diagnosis. Conclusions: We analyzed the areas of robustness and limitations of ChatGPT’s responses on the management of cirrhosis and HCC and relevant emotional support. ChatGPT may have a role as an adjunct informational tool for patients and physicians to improve outcomes.