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PubMed2026

Effect of intraoperative 40-hz gamma-frequency auditory stimulation on postoperative delirium in older adults undergoing major surgery: a randomized clinical trial protocol.

INTRODUCTION: Postoperative delirium (POD) is a common and clinically significant complication among older adults undergoing major surgery under general anesthesia. Gamma-frequency (40-Hz) auditory stimulation has demonstrated potential neuroprotective and cognition-enhancing effects, suggesting a plausible role in perioperative delirium prevention. However, direct clinical evidence supporting intraoperative 40-Hz auditory stimulation in reducing POD remains limited, warranting rigorous evaluation in a randomized trial. PATIENTS AND METHODS: This prospective, parallel-group, randomized controlled trial will enroll 550 older adults scheduled for major noncardiac, nonneurosurgical surgery under general anesthesia. Participants will be randomized in a 1:1 ratio to either the active stimulation group, receiving intraoperative 40-Hz gamma-frequency auditory stimulation delivered via headphones for 2 h following successful anesthesia induction, or the sham stimulation group, wearing headphones without active auditory output. The primary outcome is the incidence of POD on postoperative day 1 though 3, assessed using the Confusion Assessment Method (CAM) or the CAM for the ICU (CAM-ICU). Secondary outcomes include POD severity, sleep quality, pain scores, analgesic consumption, the incidence of postoperative nausea and vomiting (PONV), rescue antiemetic use, duration of post-anesthesia care unit (PACU) stay, length of hospital stay, quality of postoperative recovery, incidence of perioperative adverse events; postoperative morbidity, health-related quality of life, and all-cause 30-day mortality. DISCUSSION: This trial will determine whether intraoperative 40-Hz gamma-frequency auditory stimulation reduces the incidence of POD among older adults undergoing major surgery under general anesthesia. If efficacious, this noninvasive intervention could constitute a feasible perioperative strategy to mitigate delirium risk and enhance postoperative recovery. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2500115156).

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PubMed2026

Dexamethasone as an adjuvant to continuous erector spinae plane block for postoperative analgesia after video-assisted thoracoscopic surgery for pulmonary nodule surgery: a randomized controlled trial.

BACKGROUND: While dexamethasone is proven to enhance single-shot erector spinae plane block (ESPB), its role as an adjuvant in continuous ESPB catheters is unclear. This randomised controlled trial evaluated whether adding dexamethasone to ropivacaine improves analgesia after video-assisted thoracoscopic surgery (VATS). METHODS: 85 patients undergoing VATS with continuous ESPB were randomised to receive postoperative infusion of either 0.2% ropivacaine(C-ESPB group) or ropivacaine with 10 mg dexamethasone(D + C-ESPB group). The primary outcome was resting pain visual analog scale (VAS)at 12 h postoperatively, while secondary outcomes included QoR-15 scores, tramadol consumption, time to first analgesic requirement, postoperative adverse events, 3-month incidence of chronic pain, catheter-related complications, pain intensity at other times, and hospital stay. RESULTS: The D + C-ESPB group had significantly lower resting pain at 12 h [2.56 (1.03) vs 3.24 (1.21), mean difference -0.680, p = 0.006]; and lower coughing pain at 12 h [4.60 (1.48) vs 5.69 (1.35), mean difference 1.086, p < 0.001], with analgesic superiority sustained through 72 h. Quality of Recovery-15 scores were higher at 12 h [124.70 (12.48) vs 117.26 (12.24); mean difference -7.436, p = 0.007] and 48 h [141.60 (5.51) vs 138.98 (6.64); mean difference -2.628, p = 0.050]; Total tramadol consumption over 72 h was markedly reduce [0 (0,100) vs 100 (75,100), z = -3.807, p < 0.001], and hospital stay was shorter [Mean (SD) 6.09 (1.34) d vs 6.93 (1.55)d, p < 0.001]. The intervention did not, however, alter the 3-month incidence of chronic postsurgical pain (31% vs 34%, p = 0.756). CONCLUSION: Dexamethasone significantly enhances the analgesic efficacy of continuous ESPB, improving early pain control, recovery quality, and opioid-sparing after VATS, but does not reduce the incidence of chronic persistent surgical pain.

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PubMed2026

Systematic Review on the Effectiveness of Photobiomodulation Therapy on Enhancing Musculoskeletal Rehabilitation Outcomes after Total Knee and Hip Arthroplasty.

BACKGROUND: Total knee and hip arthroplasty (TKA/THA) effectively alleviate chronic pain and improve joint function and quality of life. However, postoperative recovery is often hindered by pain, edema, restricted range of motion (ROM), and muscle weakness, necessitating structured physical rehabilitation. Photobiomodulation Therapy (PBMT) has been proposed as an adjunct modality to enhance rehabilitation outcomes. This systematic review evaluates the efficacy of PBMT in reducing postoperative pain and edema as well as improving ROM and functional performance compared with placebo or standard physical therapy in post-arthroplasty patients. METHODS: A systematic search of PubMed, ProQuest, ScienceDirect, and Google Scholar was conducted from inception to May 31, 2025. Only prospective controlled trials assessing PBMT effects on postoperative pain, swelling, ROM, or functional performance following TKA or THA were included. Case reports, uncontrolled studies, and trials focusing on unrelated outcomes were excluded. Article selection involved title, abstract, and full-text screening, with additional studies identified through reference lists. The review is registered in PROSPERO (CRD420251123169). RESULTS: Four randomized controlled trials (RCTs; n = 133 participants) met the inclusion criteria, three studies focused on TKA, and one study examined THA. PBMT significantly improved postoperative pain and edema reduction in three trials, while two studies demonstrated enhanced ROM and functional outcomes compared with control or placebo interventions. PEDro scores ranged from 8 to 10, indicating moderate-to-high methodological quality. CONCLUSIONS: PBMT shows promising short-term benefits in reducing postoperative pain and swelling and improving functional performance after knee or hip arthroplasty. However, due to heterogeneity in treatment parameters and limited high-quality trials, conclusive evidence remains insufficient. Future large-scale RCTs with standardized PBMT parameters and extended follow-up are warranted to confirm its clinical efficacy.

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PubMed2026

The Efficacy of Erector Spinae Plane Block Versus Subcostal Transversus Abdominis Plane Block in Laparoscopic Nephrectomy: A Randomized Clinical Trial.

OBJECTIVES: This study compared the efficacy and safety of erector spinae plane block (ESPB) versus subcostal transversus abdominis plane (TAP) block in reducing postoperative pain among patients undergoing laparoscopic nephrectomy. METHODS: This randomized clinical trial enrolled 70 adult patients, ASA physical status I or II, who underwent total (radical) laparoscopic nephrectomy under general anesthesia. Patients were randomly assigned to 2 groups. Group ESPB received an ultrasound-guided ESPB at the T7 transverse process level, while group TAP received an ultrasound-guided subcostal TAP block. The primary outcome was the total amount of morphine consumed at 6 and 24 hours postoperatively. Secondary outcomes included the incidence of patients requiring opioid analgesia, time to rescue analgesia, visual analog scale of pain intensity, time to postoperative ambulation, intraoperative and postoperative hemodynamics, arterial partial pressure of oxygen to fraction of inspired oxygen (PaO 2 /FiO 2 or P /F) ratio, and incidence of complications. RESULTS: Compared with the TAP group, the ESPB group exhibited significantly lower median morphine consumption at 24 hours ( P =0.032), prolonged time to first analgesic rescue ( P =0.049), and lower incidence of rescue morphine requirement (OR=0.23; 95% CI=0.06-0.94; P =0.031), with lower visual analog scale pain scores at 12, 18, and 24 hours postoperatively ( P <0.001). The mean arterial blood pressure and heart rates were comparable between groups. No significant adverse effects from either approach. DISCUSSION: In laparoscopic nephrectomy, ultrasound-guided ESPB may safely and effectively be used to improve pain management and reduce pain intensity, with stable hemodynamics and a comparable risk of postoperative complications to the ultrasound-guided subcostal TAP block.

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PubMed2026

Patient-reported outcomes in pediatric regional anesthesia trials: current use and limitations.

PURPOSE OF REVIEW: This review examines the current use and limitations of patient-reported outcome measures (PROMs) in pediatric regional anesthesia research. Despite the increasing emphasis on patient-centered outcomes, existing pediatric outcome assessment frameworks may inadequately capture the pain experience and interference with daily living. RECENT FINDINGS: Across 17 identified randomized controlled trials and 15 ongoing studies, PROM use remains highly variable, with consistent reliance on observational pain scales such as the Face, Legs, Activity, Cry, and Consolability scale and limited incorporation of standardized, longitudinal health-related quality-of-life measures. SUMMARY: Current pediatric PROM frameworks remain fragmented, limiting comprehensive evaluation of recovery. Greater standardization and incorporation of developmentally appropriate, longitudinal outcome measures are needed to better align clinical research with meaningful patient-centered endpoints and to improve assessment of functional and psychosocial recovery.

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PubMed2026

Effects of sub-anesthetic doses of esketamine on immune function and postoperative negative emotions in acoustic neuroma patients: a randomized clinical trial.

BACKGROUND: Patients undergoing acoustic neuroma (AN) surgery often experience postoperative negative emotions, including anxiety, depression, and immune function suppression. This trial evaluated whether perioperative sub-anesthetic esketamine improves early postoperative negative emotions and immune function. METHODS: In this single-center, double-blind, randomized trial, 84 patients scheduled for AN surgery were assigned to esketamine (n = 42) or placebo (n = 42). The esketamine cohort received a continuous intravenous infusion of esketamine at 0.2 mg·kg-1·h-1 during anesthesia, followed by 1 mg·kg-1 esketamine as an adjuvant in patient-controlled intravenous analgesia (PCIA). The placebo group received saline. The primary outcome was the incidence of depression on postoperative day (POD1), defined as a Hospital Anxiety and Depression Scale-Depression subscale (HADS-D) score > 7. RESULTS: Seventy-seven patients completed the study (39 in the esketamine group, 38 in the placebo group). Esketamine significantly reduced the incidence of depression at POD1 (7.7% versus 31.6%; relative risk 0.24, 95% CI: 0.08-0.80, p = 0.008) and POD3 (0.0% versus 15.8%, relative risk 0.00, 95% CI: 0.00-0.47, p = 0.031) compared with placebo. The incidences of anxiety on POD1 and 3 and sleep disturbances on POD1 were also significantly reduced (p < 0.05). Notably, no significant differences were observed between the two groups in terms of immune function, postoperative pain scores, or intraoperative morphine equivalent. Adverse events did not differ between the groups. CONCLUSION: Perioperative sub-anesthetic esketamine reduced postoperative depression and anxiety, and improve sleep quality after AN surgery, without significant effects on early immune function or acute postoperative analgesia. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2400084537.

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PubMed2026

Machine learning-ready genomic biomarkers: ATF3 polymorphisms predict postoperative analgesic demand through AI-compatible phenotyping.

PURPOSE: To determine whether ATF3 polymorphisms can serve as genetic biomarkers for machine learning-based precision analgesia by establishing a genotype-phenotype association suitable for predictive modeling of postoperative opioid requirements. METHODS: In a prospective cohort of 167 adults undergoing abdominal surgery, ATF3 SNPs rs3122721 and rs3125293 were genotyped. A structured dataset architecture was developed to represent genetic profiles as input features for supervised learning models, enabling translational analysis of genotype‑dependent opioid consumption over 72 h. RESULTS: Patients with homozygous genotypes of the ATF3 SNPs had significantly higher opioid requirements than non‑carriers, despite reporting similar subjective pain scores. This consistent genotype‑dependent pattern provided a clinically relevant phenotype suitable for integration into predictive algorithms. CONCLUSION: ATF3 genotyping offers a promising biomarker for computationally informed precision analgesia. By linking genomic variability to clinically meaningful outcomes within a structured clinical and genomic framework, this approach supports the future development of risk-stratified clinical decision-support systems to optimize postoperative pain management.Trial registration ChiCTR1900021991, registered 30 April 2019. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at https://doi.org/10.1007/s13755-026-00480-9.

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PubMed2026

Malnutrition and adverse outcomes after spine surgery: a systematic review and meta-analysis.

BACKGROUND CONTEXT: Malnutrition is linked to adverse surgical outcomes, but its impact in spine surgery remains unclear due to inconsistent findings and heterogeneous definitions, including use of serum albumin, prealbumin, lymphocyte count, the Geriatric Nutritional Risk Index, and the Prognostic Nutritional Index. We conducted a systematic review and meta-analysis to evaluate the relationship between malnutrition and postoperative outcomes in spine surgery. PURPOSE: To systematically evaluate the association between preoperative malnutrition and postoperative outcomes in patients undergoing spine surgery. STUDY DESIGN: Systematic review and meta-analysis. PATIENT SAMPLE: Patients undergoing elective or urgent spine surgery across included observational studies comparing malnourished vs well-nourished cohorts. OUTCOME MEASURES: Primary outcomes included postoperative mortality and overall surgical complications. Secondary outcomes included infectious complications (sepsis, urinary tract infection, wound complications), delirium, reoperation, 30-day and 90-day readmission, and prolonged length of hospital stay. METHODS: A systematic search of PubMed, Embase, Cochrane Library, and Web of Science was performed on April 7, 2025, following PRISMA guidelines. Studies directly comparing postoperative outcomes in malnourished vs well-nourished spine surgery patients were included. A random-effects model generated pooled odds ratios for complications. Outcomes assessed included mortality, surgical complications, infectious outcomes, readmission, reoperation, delirium, prolonged length of stay, and wound complications. RESULTS: Of 2,851 screened articles, 37 met the inclusion criteria, encompassing 16,987 malnourished patients. Malnutrition was associated with significantly increased odds of mortality (OR: 4.05, 95% CI [2.97-5.54]), delirium (OR: 3.95, 95% CI [2.49-6.27]), sepsis (OR: 2.77, 95% CI [2.31-3.33]), surgical complications (OR: 1.79, 95% CI [1.57-2.04]), urinary tract infection (OR: 1.81, 95% CI [1.59-2.06), wound complications (OR: 2.10, 95% CI [1.80-2.45]), reoperation (OR: 1.70, 95% CI [1.46-1.97]), prolonged length of hospital stay (OR: 3.46, 95% CI [2.57-4.65]), 30-day readmission (OR: 1.59, 95% CI [1.36-1.86]), and 90-day readmission (OR: 2.13, 95% CI [1.67-2.71]). CONCLUSIONS: Malnutrition was consistently associated with adverse outcomes after spine surgery. Routine nutritional assessment and targeted preoperative optimization should be considered a standard component of perioperative spine care to help reduce postoperative complications and improve recovery.

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PubMed2026

Comparison of opioid-free versus opioid-based total intravenous anaesthesia in elderly patients undergoing short-duration surgery: a randomized controlled trial.

INTRODUCTION: Older adults who undergo short-duration surgery are vulnerable to opioid-related complications. It is uncertain whether an opioid-free total intravenous anaesthesia (OFA) can reduce these events. We aimed to determine whether OFA reduces the incidence of major postoperative adverse events compared with standard opioid-based total intravenous anaesthesia (OBA). PATIENTS AND METHODS: This single-center randomized clinical trial was conducted in China. From May to August 2025, 400 patients aged ≥60 years undergoing elective, short-duration surgery (anticipated duration of less than 90 min) were randomized 1:1 to receive either OFA (n = 200) or OBA (n = 200). The primary outcome was a composite of postoperative hypoxemia, delirium, or nausea and vomiting (PONV) within 48 h. RESULTS: A total of 400 randomized patients (mean [SD] age, 69.5 [7.0] years; 125 [31.3%] women). The primary composite outcome occurred in 50 patients (25.0%) in the OFA group and 87 patients (43.5%) in the OBA group (adjusted odds ratio, 0.40; 95% CI, 0.25 to 0.62; p < .001). Among the OFA group had a lower incidence of hypoxemia (15.0% vs 32.0%) and PONV (8.0% vs 16.0%). Intraoperative hemodynamic stability was greater in the OFA group. However, the OFA group had a higher incidence of intraoperative bradycardia (10.0% vs 3.0%; p = .005) and longer extubation times (mean, 9.5 vs 7.2 min; p < .001). CONCLUSION: These findings suggest that OFA is a viable alternative to opioid-based anesthesia for improving postoperative outcomes by reducing the incidence of hypoxemia and PONV in this population, while warranting careful management of its associated side effects. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2500102550.

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PubMed2026

Clinical effectiveness of transversus abdominis plane block versus local anaesthesia wound infiltration for postoperative pain relief after laparoscopic appendicectomy in children: A multicentre, double-blind, randomised, controlled phase III trial.

BACKGROUND: Postoperative pain relief after laparoscopic appendicectomy in children provided by transversus abdominis plane (TAP) block and local anaesthesia wound infiltration (LAWI) of trocar insertion sites has never been compared. OBJECTIVE: To investigate whether TAP block could decrease postoperative opioid requirements after laparoscopic appendicectomy in children compared with LAWI. DESIGN: Multicentre, double-blind, phase III randomised trial. SETTING: Two tertiary paediatric surgery centres. PATIENTS: Children aged 3 to 15 years admitted for laparoscopic appendicectomy. MAIN OUTCOME MEASURES: The primary outcome was the total dose of nalbuphine delivered within 24 h after surgery. Secondary outcomes were the Face Legs Activity Cry Consolability (FLACC) scale values at 1, 2, 6, 12 and 24 h, the time from levobupivacaine injection to the first dose of nalbuphine, and the time from the end of surgery to the first mobilisation. Patients received either ultrasound-guided TAP block (TAP group) or LAWI of trocar insertion sites (infiltration group) with 0.6 ml kg -1 of levobupivacaine 2.5 mg ml -1 , combined with standardised systemic multimodal analgesia including paracetamol, ketoprofen, phloroglucinol and nalbuphine. RESULTS: Forty-six and 50 patients were analysed in the TAP and infiltration groups, respectively [age: 10 [7 to 12] versus 10 [8 to 12] years; females: 16 (35%) versus 25 (50%); duration of surgery: 71 [64 to 90] versus 69 [56 to 89] min]. The primary outcome (total nalbuphine dose) was 0.2 [0.0 to 0.2] and 0.2 [0.0 to 0.2] mg kg -1 in the TAP and infiltration groups, respectively ( P  = 0.95). FLACC scale values did not significantly differ between the two groups ( P  = 0.78). Time to the first dose of nalbuphine or to first mobilisation was not significantly different between groups ( P value for log-rank test = 0.095 and 0.18, respectively). CONCLUSION: TAP block does not appear to provide a greater opioid-sparing effect than LAWI of trocar insertion sites after laparoscopic appendicectomy in children, when combined with systemic multimodal analgesia including nonsteroidal anti-inflammatory drugs. TRIAL REGISTRATION: ClinicalTrials.gov NCT04969133.

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PubMed2026

Risk Factors and Predictive Model for Postoperative High Myopia in Children Undergoing Congenital Cataract Surgery With Intraocular Lens Implantation.

PURPOSE: To identify risk factors associated with the development of high myopia following congenital cataract surgery and to establish a robust predictive model. DESIGN: Retrospective clinical cohort study. SUBJECTS: This retrospective study included 106 pediatric patients who underwent congenital cataract surgery with primary IOL implantation (mean follow-up 8.19 years). The model was externally validated in an independent cohort of 72 patients with a mean follow-up of 7.83 years. METHODS: Preoperative and postoperative ocular biometric parameters were collected. Risk factors for postoperative high myopia were analyzed using Cox proportional hazards regression, which served as the basis for model construction. The predictive performance of the model was rigorously evaluated for discrimination and calibration. Discriminative ability was quantified using Harrell's C-index and the area under the receiver operating characteristic curve (AUC). Model calibration was assessed via calibration plots by comparing predicted probabilities with actual observed outcomes. Internal validation was performed using a bootstrapping method (500 iterations) to ensure model stability and adjust for potential overfitting. RESULTS: An initial postoperative refraction of <+0.75D, and a higher IOL Power to Axial length Ratio (IOL/AL ratio) were identified as significant risk factors for the development of postoperative high myopia. Shorter preoperative axial length was associated with a greater magnitude of postoperative myopic shift. The predictive model demonstrated robust performance, achieving a C-index of 0.711 (internal validation C-index: 0.713). The area under the receiver operating characteristic curve (AUC) values for predicting high myopia at 5 and 10 years were 0.858 and 0.745, respectively. Furthermore, calibration curves demonstrated excellent agreement between the predicted and observed outcomes throughout the follow-up period. In external validation, the model achieved a C-index of 0.825, 5-year AUC of 0.833, and 10-year AUC of 0.713. CONCLUSIONS: Our analysis established that initial postoperative refraction <+0.75D, and an elevated IOL/AL ratio are key determinants of high myopia risk following surgery. Shorter preoperative axial length was associated with a greater magnitude of postoperative myopic shift. This predictive framework provides clinicians with a practical tool to optimize preoperative IOL selection and identify high-risk infants who require vigilant myopia prevention and balanced amblyopia management.

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PubMed2026

Pain outcomes of pediatric circumcision patients following administration of pre-operative ketorolac: A randomized clinical trial.

INTRODUCTION: Circumcision is a common surgical intervention, and pain is the most common complaint. Poorly managed pain can increase morbidity and reduce patient and parent satisfaction. Ketorolac, a non-steroidal anti-inflammatory drug (NSAID), provides analgesia and may be effective in reducing pain after circumcision in pediatric patients. STUDY OBJECTIVES: The primary objective was to determine the effect of pre-operative intravenous ketorolac versus normal saline placebo on parental perception of postoperative pain at 24 h. We also explored the effect of ketorolac on postoperative pain scores, incidence of bleeding, incidence of vomiting, and analgesic use. MATERIALS AND METHODS: A prospective, randomized, single-blinded trial was conducted at a single tertiary children's hospital. Patients aged 1-17 presenting for circumcision were included and randomized to either normal saline injectate or ketorolac (0.5 mg/kg, maximum 30 mg). Postoperative delirium and pain scores were recorded in the post-anesthetic care unit. Parents completed the parents' postoperative pain measure (PPPM) at 24 h. The CONSORT criteria and checklist were used to guide reporting of this randomized controlled trial. RESULTS: A total of 100 participants were included. 50 participants were in each group. Mean (SD) PPPM score 24 h after normal saline and ketorolac was 6.1 (3.4) and 5.5 (3.3), respectively for a mean difference of -0.55 points [95% CI: -1.9 to 0.83; p = 0.427]. The mean (95% CI) fixed effect size of ketorolac on post anesthetic care unit reported Face, Leg, Activity, Cry, Consolability score was -0.17 (-0.77 to 0.43, p = 0.585) points, while the mean (95% CI) effect size of ketorolac on numerical rating scale was -1.2 (-2.2 to -0.18, p = 0.026) points. DISCUSSION: Pre-operative intravenous ketorolac, compared to normal saline placebo, did not result in a difference in parental perception of postoperative pain at 24 h after circumcision surgery. As part of exploratory analyses, those receiving ketorolac had modestly lower mean immediate postoperative pain scores, likely not of clinical importance. Ketorolac has often been avoided due to concerns of increased bleeding risk, however it is important to consider that there is no substantial evidence to support this. This is the first study to our knowledge evaluating the effect of ketorolac in pediatric circumcision patients. While the PPPM score is a family centered outcome, it is an indirect measurement of pediatric pain. CONCLUSIONS: Pre-operative intravenous ketorolac was not associated with lower parental reported pain scores at 24 h compared to normal saline placebo after pediatric circumcision surgery. CLINICAL TRIAL REGISTRATION: NCT02973958.

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PubMed2026

HSK21542 for Postoperative Analgesia in Gynecological Surgery: A Pooled Post-Hoc Analysis of Two Phase III Randomized Controlled Trials.

BACKGROUND: Effective postoperative pain management in gynecological surgery is challenging because of complex visceral-somatic pain interactions and the adverse effects of conventional analgesics. HSK21542, a novel peripherally restricted kappa-opioid receptor (KOR) agonist that selectively targets visceral pain pathways enriched with KORs, may provide adequate analgesia without systemic adverse events. METHODS: We conducted a pooled post-hoc analysis of data from two phase III, multicenter, triple-blinded, randomized controlled trials (Study 301, HSK21542 vs placebo; Study 303, HSK21542 vs tramadol vs placebo). Eligible patients undergoing elective gynecological surgery were included. The primary outcome was the summed pain-intensity difference over 12 and 24 hours (SPID 12h and SPID 24h ). Secondary outcomes were pain-relief quality (proportion of patients relieved from severe pain with a pain numerical rating score ≤ 3 between 0 and 24 hours) and rescue-analgesic requirements (number of doses and time to first rescue analgesic). Adverse events were also assessed. RESULTS: A total of 370 patients were analyzed: 150 received HSK21542, 139 received a placebo, and 81 received tramadol. After inverse probability of treatment weighting (IPTW) adjustment, baseline characteristics were well-balanced across treatment groups (all standardized mean differences [SMD] <0.1; see Table 1 for 95% CIs). HSK21542 produced greater reductions in pain intensity over 12 and 24 hours than placebo (least-squares mean differences -8.1 and -16.3 for SPID 12h and SPID 24h , respectively. Both P < .001) and no statistically significant difference was observed between HSK21542 and tramadol ( P > .05). Significantly more patients in the HSK21542 group were relieved from severe pain at 0 to 12 hours (92.7% vs 82.7%, P < .001) and required fewer rescue doses at 0 to 12 hours (0.00 [IQR 0.00-1.00] vs 1.00 [IQR 0.00-2.00], P < .001) and 0 to 24 hours (0.00 [IQR 0.00-1.00] vs 1.00 [IQR 0.00-2.00], P < .001) than those in the placebo group, whereas no significant differences with tramadol both in 0 to 12 and 0 to 24 hours. HSK21542 was also associated with significantly lower incidences of nausea (24.7% vs 66.7%) and vomiting (21.3% vs 60.5%) than tramadol. Only one case of dizziness occurred in the tramadol group. CONCLUSIONS: HSK21542 could provide adequate postoperative analgesia with few adverse events in patients undergoing gynecological surgery.

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PubMed2026

Liposomal bupivacaine versus ropivacaine for surgical site infiltration in lumbar fusion: a prospective randomized controlled trial.

INTRODUCTION: Effective postoperative pain control after lumbar spine surgery remains challenging, and excessive opioid use is associated with adverse outcomes. Evidence comparing liposomal bupivacaine (LB) with conventional long-acting local anesthetics in spine surgery is limited. PATIENTS AND METHODS: In this single-center, prospective, randomized, patient- and outcome assessor-blinded trial, adult undergoing one- or two-level posterior lumbar decompression and fusion were assigned (1:1) to surgical site infiltration with either LB (266 mg) plus 25 mg plain bupivacaine (LB group) or ropivacaine (R group). The primary outcome was 72 h cumulative opioid consumption (morphine milligram equivalents, MME). Secondary outcomes included time-profile opioid consumption, pain scores, rescue analgesia, safety, and functional recovery. RESULTS: A total of 202 patients were included in the modified intention-to-treat analysis. Cumulative MME within 72 h was significantly lower in the LB group compared with the R group [43.0 (37.0, 58.0) mg vs. 58.0 (46.0, 73.0) mg], corresponding to a 22% relative reduction (GMR 0.78, 95% CI 0.71-0.85; p < 0.001). The reduction was most pronounced during 8-24 h and 24-48 h postoperatively. Overall pain scores at rest and with movement, as well as 72-h pain AUC, were lower in the LB group. No significant between-group differences were observed in rescue analgesia, adverse events and functional recovery. CONCLUSION: In patients undergoing one- or two-level posterior lumbar decompression and fusion, surgical site infiltration with an LB-based combined regimen, compared with ropivacaine monotherapy, reduced 72-h opioid consumption and cumulative postoperative pain burden without an observed increase in adverse events or impairment of early functional recovery.

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PubMed2026

Non-tobacco nicotine dependence and postoperative complications after total ankle arthroplasty: A propensity-matched cohort study.

BACKGROUND: The clinical impact of non-tobacco nicotine dependence (NTND) is poorly defined. This study evaluated the association between NTND and complications following total ankle arthroplasty (TAA). METHODS: A retrospective cohort study using the TriNetX Research Network was performed. Adults undergoing primary TAA (Current Procedural Terminology [CPT] 27702) between 2010 and 2025 were included. Patients were categorized into NTND (International Classification of Diseases, Tenth Revision [ICD-10]: F17, excluding tobacco-specific codes) and nonsmoker cohorts. Propensity score matching (1:1) yielded 939 NTND patients and 939 controls. Ninety-day medical and wound complications and ≥ 2-year mechanical outcomes were assessed. RESULTS: NTND patients had higher rates of 90-day readmission (11.7% vs 6.5%; OR 1.9), wound disruption (4.3% vs 2.6%; OR 1.7), surgical site infection (3.1% vs 1.6%; OR 2.0), and sepsis (2.4% vs 1.1%; OR 2.3). At a minimum 2-year follow-up, NTND was not associated with increased risk of mechanical complications. CONCLUSION: These findings challenge the assumption that smokeless nicotine products are benign in the perioperative setting and support incorporating NTND screening and cessation counseling into preoperative optimization protocols. Future prospective studies are warranted to further characterize the dose-dependent effects of non-tobacco nicotine exposure and to evaluate the impact of perioperative cessation strategies on outcomes following TAA. LEVEL OF EVIDENCE: IV.

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PubMed2026

Application of SPI-guided analgesia in laparoscopic gynecologic surgery: a randomized controlled trial evaluating the remifentanil-sparing effect and predictive value of time-weighted SPI.

This study aimed to achieve two primary objectives: (1) to evaluate the opioid-sparing effect of Surgical Pleth Index (SPI)-directed analgesia during surgery via a randomized controlled trial (RCT), and (2) to propose and preliminarily assess a novel dynamic metric, Threshold-based Time-Weighted SPI (Tb-TW-SPI), which integrates stimulus intensity and duration, for its predictive efficacy regarding postoperative moderate-to-severe pain. Employing an RCT combined with exploratory analysis, 61 patients undergoing elective laparoscopic gynecologic surgery were randomized into an SPI-directed analgesia group or a conventional analgesia group. The primary outcome was total intraoperative remifentanil consumption. Postoperatively, an exploratory analysis of the control group data evaluated the correlation between Tb-TW-SPI and Numeric Rating Scale (NRS) pain scores in the post-anesthesia care unit (PACU), calculating its predictive value for moderate-to-severe pain (NRS ≥ 4). Results: The SPI-directed group required significantly less intraoperative remifentanil than the conventional group [median (IQR): 5.84(5.02,6.62)vs. 6.96(5.81,8.19)µg/kg/h; P = 0.016]. Postoperative pain scores did not differ significantly between groups (P > 0.05). Exploratory analysis of the conventional analgesia group revealed that Tb-TW-SPI values were significantly higher in patients with moderate-to-severe postoperative pain (NRS ≥ 4) compared to those without (P = 0.0417).The area under the ROC curve for Tb-TW-SPI predicting this pain was 0.74 (95% CI: 0.52-0.96), with 67% sensitivity and 76% specificity at an optimal cutoff of 1210. This RCT suggests that SPI-directed analgesia can safely and moderately reduce intraoperative remifentanil consumption. Furthermore, the proposed Tb-TW-SPI metric, in this exploratory analysis, suggests potential for predicting postoperative pain, though this finding requires validation in larger cohorts with higher-frequency SPI sampling, offering a new direction for SPI interpretation. Large-scale, multicenter trials are warranted to validate the predictive utility of Tb-TW-SPI. Clinical Trial Registration, China Clinical Trial Registry: ChiCTR2400088444.

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PubMed2026

Evaluation of intravenous sedation in dental implant surgeries: A prospective cohort study.

PURPOSE: This study aimed to evaluate the impact of intravenous sedation on patient-centered outcomes during implant and bone augmentation surgeries. METHOD: A prospective observational cohort study included 40 patients undergoing placement of ≥3 implants, with or without bone augmentation. Patients underwent surgery under either intravenous sedation (n = 20) or local anesthesia alone (n = 20), according to routine clinical decision-making and patient preference. The sedation group received intravenous sedation with a multimodal regimen comprising remimazolam, dexmedetomidine, alfentanil, and low-dose esketamine, whereas the control group received local anesthesia only. Patient-reported outcome measures, hemodynamic parameters (SBP, DBP, HR, SpO2), postoperative pain (0-10 scale), and OHRQoL (OHIP-14) were recorded from baseline through 7 days post-surgery. RESULTS: Intravenous sedation was associated with significantly lower intraoperative pain (0.5 [IQR: 0∼2.75] vs. 3.25 ± 2.40, p = 0.003), anxiety (1 [IQR: 0∼2.75] vs. 4 [IQR: 3∼6], p = 0.001), and experienced discomfort (2 [IQR: 1∼3.75] vs. 4.15 ± 2.16, p = 0.016), and shortened perceived treatment duration (2.90 ± 2.34 vs. 5 [IQR: 4∼5], p = 0.020). Early postoperative pain was lower in the sedation group from Days 1-4 (p = 0.003-0.010). Hemodynamic parameters were more stable under sedation, with lower SBP (116.42 ± 13.32 vs. 144.11 ± 17.42 mmHg, p < 0.001), DBP (73.21 ± 10.28 vs. 82.37 ± 11.03 mmHg, p = 0.012), and HR (71.00 [IQR: 62.50∼79.25] vs. 85.00 ± 10.72 bpm, p = 0.021). OHRQoL scores favored the sedation group in swallowing, diet, malaise, and daily activities, particularly during the first three postoperative days (p=0.006-0.040). CONCLUSION: Intravenous sedation may enhance the patient experience during implant and/or bone augmentation procedures by reducing intraoperative pain and anxiety, improving hemodynamic stability, and promoting better early-postoperative recovery and OHRQoL. These findings suggest that intravenous sedation provides a safe and effective alternative for implant dentistry surgery, particularly for anxious or pain-sensitive individuals.

Humans↗

PubMed2026

Effect of Perioperative Sucralfate Administration on Pain Control After Tonsillectomy: A Systemic Review and Meta-Analysis.

OBJECTIVES: This study evaluated the efficacy of perioperative intraoral sucralfate in reducing postoperative pain following tonsillectomy through a systematic review and meta-analysis. METHODS: A comprehensive search of PubMed, SCOPUS, Embase, Web of Science, and Cochrane up to September 2025 identified 13 studies comparing perioperative intraoral sucralfate with placebo or no treatment. Outcomes included throat pain, otalgia, swallowing pain, analgesic consumption, and perioperative morbidities. RESULTS: Sucralfate increased the proportion of patients reporting no or mild throat pain and otalgia, improved mucosal healing at 5 to 7 days, and reduced throat pain, swallowing pain, otalgia, analgesic use, and time to resume >50% of a regular diet. No significant differences were observed in postoperative bleeding or nausea/vomiting. CONCLUSION: Perioperative intraoral sucralfate may be an effective adjuvant therapy that improves postoperative pain control, enhances wound healing, reduces analgesic requirements, and facilitates earlier dietary resumption after tonsillectomy.

Humans↗