Kuang-I Cheng

Background: Postoperative nausea and vomiting are common complications after anesthesia. However, vomiting represents a clinically distinct and objectively measurable endpoint. Objective: This study aimed to develop and internally validate predictive models for postoperative vomiting within 24 hours using structured perioperative data and unstructured clinical text, while introducing a structured framework that separates feature construction from interpretability using large language models (LLMs). Methods: We analyzed 33,460 anesthesia records from a single center (2019‐2022). Two temporally defined prediction tasks were constructed to reflect real-world clinical decision-making and prevent information leakage: a preoperative model using variables available before anesthesia induction, and a perioperative model using variables available up to the end of surgery. Structured data were modeled using machine learning algorithms (logistic regression, Extreme Gradient Boosting, Light Gradient Boosting Machine [LightGBM]). Unstructured clinical text was incorporated through a deterministic, concept-driven preprocessing pipeline, where LLMs were used solely for normalization (temperature=0) without feature generation, followed by rule-based concept mapping and feature encoding. Post hoc interpretability was further supported using an LLM-based Question Answering Chain module. Model performance was evaluated using receiver operating characteristic-area under the curve (AUC), precision-recall AUC, calibration metrics, and threshold-based operating characteristics. Classification thresholds were selected using the Youden J statistic, and all metrics were reported with 95% CIs derived from bootstrap resampling. Decision curve analysis was performed to assess clinical utility. Results: A total of 33,460 surgical procedures were included, of which 3607 (10.8%) experienced postoperative vomiting within 24 hours. In the preoperative task, LightGBM achieved an AUC of 0.729 (95% CI 0.706‐0.749), compared with 0.610 (95% CI 0.588‐0.632) for the Apfel score. In the end-of-surgery task, LightGBM achieved an AUC of 0.735 (95% CI 0.714‐0.757). At the Youden-optimal threshold, the negative predictive value exceeded 0.95 across all models. Decision curve analysis demonstrated positive net benefit across clinically relevant threshold probabilities. Incorporating text-derived features provided modest improvements, while LLM-based explanation modules generated structured, natural-language explanations intended to enhance interpretability without substantially improving predictive performance. Conclusions: Machine learning models can effectively predict postoperative vomiting within 24 hours using perioperative data. The proposed framework demonstrates that LLMs can be integrated in a controlled and reproducible manner—restricted to deterministic normalization and post hoc reasoning—to generate natural-language explanations intended to enhance the interpretability of model predictions, without introducing information leakage or altering predictive modeling. As no formal clinician-based evaluation was conducted, this interpretability benefit cannot yet be objectively confirmed, and the generated explanations should be regarded as a useful interpretability aid to be validated in future clinician-centered studies. External, multicenter validation is required before broader clinical applicability can be assumed.

Schwann cells (SCs) support axonal function and promote nerve regeneration. This study investigated how various glucose concentrations influence SC viability, oxidative stress, and autophagy, which contribute to diabetic neuropathy. RSC96 SCs were cultured under five glucose conditions (0, 2.5, 5.5, 50, or 100 mM) for 24, 48, and 72 h. Cell viability was assessed by MTT; ROS levels were determined by DCFDA staining, and apoptosis and ER stress markers, as well as autophagy‐related proteins were assessed by Western blotting. Autophagic flux was also analyzed using bafilomycin A1 and Cyto‐ID. The results revealed time‐dependent increases in cell death across all glucose conditions, especially under deprivation and low glucose (LG) conditions. ROS, CHOP, Bax, and cleaved caspase‐3 levels increased from 24 to 72 h. The initial increase in the LC3B‐II/I ratio indicated that autophagy was overactivated under glucose deprivation or LG conditions but impaired by 72 h, as indicated by reduced Lamp‐2 expression. High glucose conditions led to early and persistent autophagy suppression, with minimal autophagic flux and vacuole formation. These findings demonstrate that SCs are sensitive to glucose levels and undergo distinct autophagic impairments through different mechanisms under persistent low or high glucose environments.

Multimodal analgesia (MMA) combines different analgesic methods, such as non-steroidal inflammatory drugs (NSAIDs), acetaminophen, and regional anesthesia techniques, to optimize pain control while minimizing opioid use. Dinalbuphine sebacate (DS), a long-acting prodrug of nalbuphine, was chosen due to its potential to enhance MMA strategies. The aim of this study is to evaluate the effectiveness of DS in MMA for video-assisted thoracoscopic surgery (VATS). Sixty participants were randomly and equally assigned to either the MMA regimen containing DS (DS group) or placebo (placebo group). After anesthesia induction, all participants received ultrasound-guided thoracic paravertebral block (TPVB), and DS or placebo was injected into the gluteus medius muscle on the operated side. Intravenous patient-controlled analgesia (IVPCA) with fentanyl was provided for breakthrough pain postoperatively. The primary outcome was postoperative fentanyl consumption over three days. Statistical tests included Student’s t-test, chi-square test, and Fisher’s exact test. Finally, 57 participants were assigned to either the DS group (n = 28) or the placebo group (n = 29). The mean fentanyl consumption over three days was significantly lower in the DS group (283 ± 70 µg) compared to the placebo group (708 ± 190 µg, P < 0.001). Pain interference with daily life was significantly lower in the DS group at one week (28.57% vs. 86.2%, P < 0.001) and one month postoperatively (10.71% vs. 48.28%, P = 0.003). Pain intensity during movement was significantly lower in the DS group at one week (2.07 ± 0.61 vs. 4.00 ± 0.56, P < 0.001) and one month (0.64 ± 0.35 vs. 2.10 ± 0.4, P < 0.001). By providing superior analgesia, reducing opioid requirements, improving functional recovery and its long-lasting effect after discharge, DS enhanced postoperative MMA for VATS. ClinicalTrials.gov Identifier, NCT04962152; Date: 14/07/2021.

Zanthoxylum species have long been utilized in traditional medicine; among their various properties, they provide an analgesic effect. Central to this medicinal application are alkamides, a class of alkaloids characterized by their unsaturated fatty acid chains. These compounds are particularly noted for their distinctive alleviation of tingling and numbing effects, which are beneficial in dental pain management and local anesthesia. This review synthesizes the existing phytochemical research on alkamides derived from 11 Z. species, focusing on their chemical properties, pharmacodynamics and clinical implications. The analysis includes an examination of the structure–activity relationships (SARs), pharmacokinetics and mechanisms by which these compounds modulate sensations such as pungency and numbness, contributing to their analgesic and local anesthetic efficacy. This systemic review identifies significant research gaps, including the need for comprehensive evaluations of alkamide efficacy, detailed explorations of their pharmacological mechanisms and expanded clinical applications. These areas represent key opportunities for future investigations to enhance the understanding and utilization of alkamides in medical treatments.

(1) Background and Objectives: Catheter-related bladder discomfort (CRBD), a common and distressing consequence of indwelling urinary catheters, can significantly impact postoperative recovery. This study aimed to determine the effectiveness of bladder irrigation with a 0.05% lidocaine normal saline solution for the prevention of CRBD following transurethral surgery. (2) Materials and Methods: In this randomized, double-blind, placebo-controlled trial, patients were assigned to either a control group receiving normal saline or a treatment group receiving 0.05% lidocaine (2% lidocaine 25 mL in 1000 mL saline) for bladder irrigation. Both groups were administered fentanyl (1 μg/kg) for analgesia at the end of the procedure. The primary endpoint was the assessment of the incidence and severity of CRBD upon awakening within the first 6 h postoperatively, using a four-grade scale based on the patients’ reports of discomfort. (3) Results: Out of 79 patients completing the study, the incidence of moderate to severe CRBD was significantly lower in the lidocaine group (5.1%, 2/39) compared to the control group (25%, 10/40) at 10 min after waking from anesthesia (p = 0.014). Furthermore, the lidocaine group experienced significantly less CRBD at 1 and 2 h postoperative (2.6% and 0%, respectively) compared to the control group (20% and 10%, respectively) (p = 0.015, p = 0.043), with no significant differences at 6 h (p = 0.317). (4) Conclusions: The results suggest that bladder irrigation with 0.05% lidocaine reduces the occurrence of moderate to severe CRBD by nearly 80% in the initial 2 h postoperative period after transurethral surgery.

This study investigated the effects of cilostazol on motor dysfunction, spinal motor neuron abnormalities, and schwannopathy in rats with diabetes. Diabetes mellitus (DM) was induced in rats via femoral intravenous streptozotocin (STZ) injection (60 mg/kg). After successful DM induction, cilostazol was administered on day 15 via oral gavage (100 mg/kg/day) for 6 weeks until sacrifice. Behavioral assays, including motor function, were performed weekly. The sciatic nerve, L5 spinal cord, and spinal ventral root were collected to evaluate the expression of the glial fibrillary acidic protein (GFAP), myelin protein zero (P0), and choline acetyltransferase (ChAT) by immunofluorescence and Western blotting. DM rats displayed decreased running speeds, running distances, and toe spread but increased foot pressure. In addition, loss of non-myelinating Schwann cells and myelin sheaths was observed in the sciatic nerve and L5 spinal ventral root. Reduced numbers of motor neurons were also found in the L5 spinal ventral horn. Cilostazol administration significantly potentiated running speed and distance; increased hind paw toe spread; and decreased foot pressure. In the sciatic nerve and L5 spinal ventral root, cilostazol treatment significantly improved non-myelinated Schwann cells and increased myelin mass. ChAT expression in motor neurons in the spinal ventral horn was improved, but not significantly. Cilostazol administration may protect sensorimotor function in diabetic rats.

Background and Objectives: Optimal opioid analgesia is an excellent analgesia that does not present unexpected adverse effects. Nalbuphine, acting on the opioid receptor as a partial mu antagonist and kappa agonist, is considered a suitable option for patients undergoing laparoscopic surgery. Therefore, we aim to investigate the appropriate dosage of nalbuphine for post-operative pain management in patients with laparoscopic cholecystectomy. Materials and Methods: Patients were randomly categorized into low, medium, and high nalbuphine groups. In each group, a patient control device for post-operative pain control was programed with a low (0.05 mg/kg), medium (0.10 mg/kg), or high (0.20 mg/kg) nalbuphine dose as a loading dose and each bolus dose with a lockout interval of 7 min and without background infusion. Primary and secondary outcomes included the post-operative pain scale and nalbuphine consumption, and episodes of post-operative opioid-related adverse events and satisfactory scores. Results: The low-dosage group presented a higher initial self-reported pain score in comparison to the other two groups for the two hours post-op (p = 0.039) but presented lower nalbuphine consumption than the other two groups for four hours post-op (p = 0.047). There was no significant difference in the analysis of the satisfactory score and adverse events. Conclusions: An appropriate administration of nalbuphine could be 0.1 to 0.2 mg/kg at the initial four hours; this formula could be modified to a lower dosage (0.05 mg/kg) in the post-operative management of laparoscopic cholecystectomy.

Background and Objective: Our previous study demonstrated that consistent treatment of oral cilostazol was effective in reducing levels of painful peripheral neuropathy in streptozotocin-induced type I diabetic rats. As diabetic neuropathy is characterized by hyperglycemia-induced nerve damage in the periphery, this study aims to examine the neuropathology as well as the effects of cilostazol treatments on the integrity of peripheral small nerve fibers in type I diabetic rats. Materials and Methods: A total of ninety adult male Sprague-Dawley rats were divided into the following groups: (1) naïve (control) group; (2) diabetic rats (DM) group for 8 weeks; DM rats receiving either (3) 10 mg/kg oral cilostazol (Cilo10), (4) 30 mg/kg oral cilostazol (Cilo30), or (5) 100 mg/kg oral cilostazol (Cilo100) for 6 weeks. Pain tolerance thresholds of hind paws toward thermal and mechanical stimuli were assessed. Expressions of PGP9.5, P2X3, CGRP, and TRPV-1 targeting afferent nerve fibers in hind paw skin and glial cells in the spinal dorsal horn were examined via immunohistochemistry and immunofluorescence. Results: Oral cilostazol ameliorated the symptoms of mechanical allodynia but not thermal analgesia in DM rats. Significant reductions in PGP9.5-, P2X3-, CGRP, and TRPV-1-labeled penetrating nerve fibers in the epidermal layer indicated denervation of sensory nerves in the hind paw epidermis of DM rats. Denervation significantly improved in groups that received Cilo30 and Cilo100 in a dose-dependent manner. Cilostazol administration also suppressed microglial hyperactivation and increased astrocyte expressions in spinal dorsal horns. Conclusions: Oral cilostazol ameliorated hyperglycemia-induced peripheral small nerve fiber damage in the periphery of diabetic rats and effectively mitigated diabetic neuropathic pain via a central sensitization mechanism. Our findings present cilostazol not only as an effective option for managing symptoms of neuropathy but also for deterring the development of diabetic neuropathy in the early phase of type I diabetes.