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Tethered spinal cord syndrome (TSCS) is a neurological disorder characterized by tissue attachments limiting spinal cord movement, which can result in the conus medullaris terminating at a level lower than the typical L1. This abnormality can cause significant complications during spinal anesthesia due to the risk of injury at the traditional puncture sites of L4-L5. This case report discusses the anesthetic management of a 65-year-old female patient diagnosed with TSCS with her spinal cord extending to L5-S1. She presented for a right total knee replacement. The patient had a history of successful spinal anesthesia for her previous left knee replacement but was apprehensive about repeating the procedure due to her spinal anatomy and the associated risks. A thorough preoperative assessment was conducted with this patient. This included a detailed MRI review by a radiologist and a neurosurgeon, which highlighted the risks associated with spinal anesthesia. Given the minimal cerebrospinal fluid around critical levels of the spinal cord, the risk of injury during spinal anesthesia was significant. After discussion with the patient about the risks and benefits of each anesthetic option, the care team and patient jointly decided that general anesthesia would offer the safest approach. General anesthesia was administered successfully with standard intraoperative monitoring and airway management. A preoperative adductor nerve block was also performed to manage postoperative knee pain. The patient emerged from anesthesia without complications, with stable vital signs and good neurovascular function. The interdisciplinary approach and careful preoperative planning were crucial to achieve a positive outcome in this case. This case highlights the importance of individualized anesthetic planning for patients with TSCS. It underscores the need for thorough preoperative assessment and patient-centered care to determine the safest anesthetic approach. This report also reviews the mechanisms of spinal cord injury during neuraxial anesthesia in TSCS, discusses epidural anesthesia as an alternative, and synthesizes evidence-based recommendations for preoperative assessment in the absence of formal guidelines. Further research and the development of formal guidelines for anesthetic management in TSCS are warranted to improve patient safety and outcomes.
Nonsurgical periodontal treatment improves clinical parameters; however, the procedure is often associated with patient discomfort. Pain control should be considered during periodontal instrumentation. This study evaluated pain perception during periodontal instrumentation using computerized anesthesia versus a noninvasive lidocaine/prilocaine gel. A parallel, blinded, randomized, clinical trial included 76 volunteers receiving either invasive anesthesia with a computerized device, or noninvasive anesthesia with lidocaine/prilocaine gel during nonsurgical periodontal instrumentation. Pain perception was assessed using an 11-point Numerical Rating Scale and anxiety with the Modified Dental Anxiety Scale. Anesthetic supplementation needs were recorded, and hemodynamic parameters were measured before and after anesthesia. Statistical analyses used the t-test or Mann-Whitney test for quantitative variables. Qualitative variables were analyzed using the Chi-square test (α = 0.05). Participants included 45 women and 31 men (mean age of 44.2 ± 12.9 years), with no significant differences in age or sex between groups. Pain intensity was similar between groups. Anxiety was similar among participants, most having low anxiety (P > 0.05). The need for supplementary anesthesia differed significantly between groups. All patients (38; 100%) in the noninvasive group required additional anesthesia. In the invasive group, only nine patients (24%) required additional anesthesia (P < 0.001). Systolic and diastolic blood pressure, along with oxygen saturation, remained stable, with no relevant variations among the study groups. Both techniques provided similar pain control during periodontal instrumentation; however, the noninvasive gel required significantly more supplementary anesthesia in comparison with the computerized-controlled system. Pretreatment anxiety levels were low and comparable between groups.
Positive-pressure ventilation can precipitate an immediate fall in arterial blood pressure during general anesthesia, but this response is usually recognized only after controlled ventilation has already been initiated and is then interpreted retrospectively. We propose a different framework for dogs and cats: a brief airway-pressure challenge during spontaneous breathing may serve as a deliberate, reversible bedside probe of hemodynamic vulnerability to subsequent positive-pressure ventilation. The aim of this article is to articulate an interpretive, hypothesis-generating framework rather than to provide a validated protocol or an immediately deployable clinical test. In this view, the immediate arterial pressure response is interpreted not as a specific diagnostic sign or a simple test of circulating volume adequacy, but as an integrated cardiopulmonary stress response. Its meaning may be shaped by preload sensitivity, right ventricular afterload sensitivity, tricuspid regurgitation, pulmonary vascular burden, anesthetic state, myocardial reserve, and respiratory mechanics. Framing the maneuver in this way shifts attention from incidental observation to proactive interpretation and may help clinicians anticipate whether positive-pressure exposure is likely to be well tolerated or to warrant greater caution, closer monitoring, and more deliberate circulatory preparation. The framework also gives additional conceptual value to preserving spontaneous breathing before mandatory controlled ventilation, because this phase provides an interpretive window before the circulation is fully exposed to sustained positive-pressure ventilation. At the same time, this concept is not presented as a validated diagnostic test or treatment algorithm. Nor is it intended to recommend routine clinical implementation of the airway-pressure challenge as a ventilation method prior to technical standardization and prospective validation. Its clinical interpretation is context dependent and is best suited to settings in which immediate arterial pressure changes can be followed continuously, preferably with invasive arterial pressure monitoring. By reframing airway-pressure-associated hypotension as a structured challenge rather than a purely incidental event, this conceptual model provides a basis for future physiologic validation while supporting more deliberate bedside interpretation of cardiopulmonary vulnerability in veterinary anesthesia.
Background  Postoperative pain management in children remains a significant challenge due to developmental differences in pain perception, reporting, and communication. However, limited evidence exists regarding age-specific predictors of severe pain and patient satisfaction among preschool and school-age children, particularly when perioperative, psychological, and analgesic-related factors are integrated. Despite advances in multimodal analgesia, a substantial proportion of pediatric patients continue to experience inadequate postoperative pain relief. Objectives To evaluate postoperative pain trajectories, identify predictors of severe pain, and assess factors associated with satisfaction in pediatric patients undergoing elective surgery, with stratification by developmental age groups (preschool versus school-age). Methods This prospective multicenter observational cohort study included 325 children aged three to 12 years undergoing elective surgery under general anesthesia, with or without regional anesthesia (RA). Patients were categorized into preschool (3-6 years, n=175) and school-age (6-12 years, n=150) groups. Pain intensity was assessed at predefined time points during the first 24 postoperative hours using age-appropriate validated scales: the Face, Legs, Activity, Cry, Consolability (FLACC) scale for preschool children and the Numerical Rating Scale (NRS) for school-age children. Severe pain was defined as NRS ≥7/10. Satisfaction with pain management was recorded on a 0-10 scale. Multivariable logistic regression identified independent predictors of severe pain, while linear regression evaluated factors associated with patient satisfaction. Results Pain scores peaked in the early postoperative period and declined significantly over time (P<0.001). Severe pain occurred in 26.5% of patients, with no significant difference between groups (P=0.324). School-age children reported higher pain immediately postoperatively, whereas preschool children exhibited higher pain scores later during recovery. Independent predictors of severe pain included higher early postoperative pain, pain at discharge, preoperative anxiety, and the need for additional analgesia. In contrast, pre-incisional local anesthetic infiltration (LAI), RA, premedication, and preoperative education were associated with lower odds of severe pain (all P<0.05). Satisfaction scores were high (mean 8.1±1.1) and were positively associated with effective pain relief, use of regional techniques, and patient/parent involvement in care. Conversely, persistent severe pain, higher early postoperative pain, and the need for additional analgesia were associated with lower satisfaction. Regression models demonstrated strong predictive performance, with Nagelkerke R² values up to 0.884 and an adjusted R² of 0.434. Conclusion Postoperative pain outcomes in children are predominantly associated with modifiable perioperative factors rather than age alone. Early pain control, multimodal analgesia, RA, and patient-centered strategies, including preoperative education and shared decision-making, are consistently associated with improved pain outcomes and satisfaction. These findings support the development of risk-stratified, individualized approaches to pediatric perioperative pain management.
The Hall technique (HT) uses elastomeric orthodontic separators (EOSs) and stainless steel crowns (SSCs). Recent research highlighted that HT was reported to cause "procedural pain." To assess bilateral HT EOSs and SSCs "procedural pain," and to evaluate the immediate effect of benzocaine 20% topical anesthesia gel (BZG) on child-perceived pain levels post-EOSs placement. A preregistered randomized controlled, split-mouth, single-blinded pilot feasibility trial (ClinicalTrials.gov ID NCT06272903) was conducted in children (N = 32) requiring bilateral HT-SSCs after BZG/placebo (both strawberry flavored) were flossed interdentally prebilateral EOSs placement. Immediate child/parent proxy pain scores post-EOSs placement (n = 104) and SSC (n = 64) cementation were recorded [using the Wong-Baker faces pain rating scale (WBFS)]. Statistical analysis-Wilcoxon signed-rank test. Significance level set at p < 0.05. Bilateral SSCs placement resulted in low child-perceived pain compared to bilateral EOSs placement (p = 0.001). BZG significantly reduced immediate child pain perception when four EOSs (two mesial and two distal) were placed per child (p = 0.045), but this was not significant when two EOSs per child were placed. Separator load/number was related to pain; pain perception was significantly higher when two placebo EOSs were placed per tooth compared to one placebo EOS per tooth (p = 0.045). In children receiving bilateral HT-SSCs, procedural pain was related to EOSs placement rather than HT-SSC cementation. When using four EOSs in children receiving bilateral HT-SSCs, BZG reduced immediate pain perception. This pilot feasibility study paves the way for a larger trial. Sura SK, Kowash M, Salami A, et al. Procedural Pain, Hall Technique Crowns and Separators: A Randomized Controlled Clinical Pilot Feasibility Study. Int J Clin Pediatr Dent 2026;19(3):357-367.
Autism spectrum disorder (ASD) presents significant challenges in dental practice due to impairments in communication, sensory processing, and behavioral regulation. This case report describes the management of a five-year-old male child with ASD who exhibited anxiety, hypersensitivity to auditory stimuli, and limited cooperation during dental visits. An individualized, non-pharmacological behavioral approach was implemented, including desensitization, the tell-show-do technique, non-verbal communication, caregiver involvement, and environmental modifications aimed at reducing sensory overload. Treatment was conducted over multiple visits, initially focusing on behavioral adaptation before progressing to preventive and restorative procedures. The child demonstrated progressive improvement in tolerance and cooperation, allowing initiation and maintenance of intraoral dental treatment without the use of sedation or general anesthesia. This case highlights the effectiveness of individualized behavioral management techniques in facilitating and sustaining cooperation and improving clinical outcomes. It also emphasizes the importance of a child-centered approach, consistency in clinician behavior, and caregiver support in managing children with ASD in the dental setting.
Radial artery catheterization (RAC) remains challenging, with a high failure rate. This study investigated whether ultrasound-measured radial artery (RA) diameter could predict RAC failure in patients undergoing major cardiac or vascular surgery. Consecutive patients scheduled for major cardiac or vascular surgery were prospectively included. Ultrasound images of the left RA were acquired by one operator, while a second operator, blinded to these images, performed RAC using the palpation method. RAC failure was defined as three or more attempts, a change in operator, or cannulation site. All ultrasound images were subsequently analyzed by an expert vascular physician, also blinded. RA internal diameter and depth were measured. Intra- and inter-observer reproducibility were assessed. Of 247 patients, 58 (23%) experienced RAC failure. Absent or weak radial pulse (OR 6.36, 95% CI 2.59-15.65; p < 0.001), female sex (OR 2.55, 95% CI 1.36-4.77; p = 0.003), and wrist circumference <18 cm (OR 1.96, 95% CI 1.08-3.54; p = 0.03) each significantly increased RAC failure risk. The RA internal diameter was significantly smaller in the failure group (1.9 ± 0.4 vs 2.1 ± 0.4 mm, p < 0.01). RA was also deeper in the failure group (3.4 ± 1.6 vs 2.9 ± 1.1 mm, p = 0.05). The area under the curve for RA internal diameter to predict RAC failure was 0.62 (95% CI 0.53-0.70, p = 0.007), with an optimal threshold of 1.8 mm. RAC failure prolonged anesthesia induction and doubled the risk of hematoma (p < 0.001). Intra- and inter-observer agreement for RA internal diameter were excellent (ICC 0.86, 95% CI 0.78-0.92 and 0.94, 95% CI 0.91-0.97, respectively). A small RA internal diameter significantly increases RAC failure risk. These findings should inform cannulation site selection, technique, and operator choice to improve procedural success and patient safety.
High-quality neonatal imaging often necessitates sedation or anesthesia to minimize motion artifacts. However, procedural sedation for non-painful pediatric examinations outside the operating room presents unique challenges due to their distinct cardiopulmonary physiology and drug metabolism. Although remimazolam is associated with minimal hemodynamic and respiratory effects in adults, evidence supporting its use in neonatal MRI remains limited. We report the first successful application of remimazolam for MRI sedation in an early-term neonate (37 ⁴⁄₇ weeks' gestational age, 2.9 kg). After unsuccessful non-pharmacologic measures and intranasal dexmedetomidine, intravenous remimazolam (0.1 mg/kg) produced adequate sedation within 1 min, allowing completion of a 17-minute MRI examination while preserving hemodynamic and respiratory stability. This case highlights potential utility of remimazolam s a rescue sedative for neonatal MRI sedation. Comprehensive multicenter studies are warranted to evaluate its safety, efficacy, and role in clinical practice.
To investigate the anxiety pattern and its association with perceived pain at different perioperative stages of dental implant surgeries in China, and identify key influencing factors of anxiety. A prospective observational perioperative study was conducted on 506 implant patients in Changsha Stomatological Hospital from January 2025 to June 2025. Patients assessed their current level of dental anxiety at each of five time points: pre-surgery night (T1), hospital waiting period (T2), local anesthesia administration (T3), implant placement procedure (T4), and post-surgery (T5). Pain perception was evaluated by patients using the Numerical Rating Scale (NRS) on the night before surgery, during surgery, and after surgery. Repeated-measures ANOVA, independent sample t-tests, binary logistic regression, and Kruskal-Wallis test were used for analysis. Anxiety levels peaked at T3 (2.61 ± 0.98) and T4 (2.51 ± 1.05), then decreased significantly at T1 (2.38 ± 1.06), T2 (2.21 ± 0.97), and T5 (1.43 ± 0.72). Predicted pain, intraoperative pain, and postoperative pain were significantly correlated with anxiety. Preoperative pain was not significantly associated with anxiety. Female (OR = 2.60), elderly patients (36-50 years old, OR = 2.40 51-72 years old, OR = 2.19), mandibular implant (OR = 1.81), and bimaxillary implant (OR = 9.63) are factors associated with increased odds of anxiety. The model showed acceptable discrimination (AUC = 0.704, 95% CI 0.658-0.750) and calibration (Hosmer-Lemeshow p = 0.42). Dental anxiety peaks during invasive procedural phases. Gender, age, implant location, and perceived pain degree are key influencing factors. Targeted interventions for high-risk groups and effective pain management can help mitigate anxiety and improve perioperative care quality.
Previous studies have shown that ovariectomy can alter bone structure, especially in the maxilla, as well as the periodontal ligament at the molecular level, and lead to cementum accumulation in the apical region. The present study was conducted to elucidate the molecular mechanisms involved. For the experiment, 12 BALB/c mice were randomly assigned to two groups: a sham surgery group and an ovariectomy group. In the sham surgery group, the ovaries were exposed and then repositioned without removal, whereas in the ovariectomy group, the ovaries were surgically excised. Twelve weeks postsurgery, the mice were sacrificed by an overdose of general anesthesia. Subsequently, the mandibles and maxillae were dissected for histological analysis. Samples were examined under a Nikon® microscope using ToupView to measure the periodontal ligament (×100) and ImageJ software for cell counting (×400). The ovariectomy group exhibited an increase in osteoclastic cell number, particularly in the mesial alveolar crest and the interradicular bone of the maxillary and mandibular regions. In addition, within the same group, widening of the periodontal ligament fibers, dilation of blood vessels, structural alterations in the periodontal ligament, as well as cementum accumulation in the apical region, were observed. Estrogen deficiency increases the number of osteoclasts, alters their orientation, widens the periodontal ligament, and leads to the accumulation of apical cementum.
Rhabdomyolysis is the acute necrosis of striated skeletal muscle, with release of its constituents into the extracellular space and circulation. Acute muscle pain (myalgia), weakness, and edema are associated with serum levels of the muscle enzyme creatine kinase (CK) above 1,000 IU/L or 5 times the upper limit of the normal value. This narrative review provides an overview of the clinical and laboratory findings, etiology, treatment, and prevention of rhabdomyolysis in humans. Additionally, we highlighted the main syndromes and muscular disorders associated with rhabdomyolysis: 1. Clinical syndromes: neuroleptic malignant syndrome, serotoninergic syndrome, sympathomimetic syndrome, malignant hyperthermia, and anesthesia-induced rhabdomyolysis; and 2. Myopathies: toxic myopathies, idiopathic inflammatory myopathies, muscular dystrophies, ion channel diseases, glycogen storage diseases, fatty acid beta oxidation defects, and mitochondrial myopathies.
A 7-year-old male patient presented to Jinan Mingshui Eye Hospital (Jinan, China) in June 2025 with a 3-month history of a progressively enlarging mass on the right upper eyelid. The lesion was asymptomatic, with no associated pain, redness or discharge. Physical examination revealed a well-defined, smooth, yellow-red, round mass measuring ~6x5x5 mm at the medial canthus of the right upper eyelid, adjacent to the upper lacrimal punctum. Under general anesthesia, the tumor was completely excised in June 2025. Histopathological examination showed squamous epithelium overlying proliferations of small spindle cells, mitotic figures and scattered Touton-like giant cells. Immunohistochemistry revealed positive staining for CD68, CD163, S-100, CD1a, CD10 and anaplastic lymphoma kinase (ALK), with a Ki-67 proliferation index of ~10%. A diagnosis of ALK-positive epithelioid fibrous histiocytoma (EFH) was established. Postoperative recovery was uneventful, with no recurrence observed during a 6-month follow-up period. This case highlights an unusual presentation of EFH in a pediatric eyelid, where a rare tumor that occurred in the eyelid of a 7-year-old child was accurately diagnosed through a set of immunohistochemical panels containing tissue cell markers (CD68 and CD163), melanoma cell markers (S-100), dendritic cell markers (CD1a), mesenchymal cell markers (CD10) and ALK.
Video-assisted thoracoscopic surgery (VATS) offers numerous advantages over open surgery; nevertheless, it remains associated with significant postoperative pain. Multiple regional anesthesia techniques have been explored, and the serratus anterior plane block (SAPB) has emerged as a promising option; however, evidence on the use of continuous SAPB infusion for quality of recovery (QoR-40) remains limited. We hypothesized that continuous SAPB infusion, combined with multimodal analgesia, could improve QoR-40 after VATS. In this prospective, double-blind, randomized controlled trial, adults undergoing elective VATS received an infusion of either 0.2% ropivacaine or saline via a SAPB catheter, in addition to standardized multimodal analgesia. The primary outcome was the QoR-40 score on postoperative day (POD) 1. Secondary outcomes included QoR-40 scores on POD 2-4, pain scores, opioid consumption in intravenous morphine milligram equivalents (IV MME), length of hospital stay (LOS), complications, and 30-day readmission. A total of 173 patients were analyzed (SAPB: n=88; control: n=85). Median QoR-40 scores on POD 1 were higher in the SAPB group (176 (166-184) vs 172 (159-183); p=0.1036), and remained higher across POD 2 to 4, although not statistically significant. SAPB significantly reduced opioid consumption in recovery (8.0±7.4 vs 10.6±9.3 IV MME; p=0.0388) and on POD 1 (12.73±10.75 vs 16.45±12.17 IV MME; p=0.0349). LOS was also lower but not statistically significant by 0.8 days (2.69±1.76 vs 3.50±4.01; p=0.0872). Pain scores, complications, and 30-day readmissions were similar between groups. In this prospective, double-blind, randomized, placebo-controlled trial, continuous SAPB catheter infusion did not improve the primary outcome (QoR-40), and the observed differences in secondary outcomes should be interpreted as exploratory. Larger studies are needed to confirm effects on patient-reported recovery.
To prospectively assess the clinical outcomes and safety of microsurgical denervation of the penis (MSDP) for treatment of lifelong premature ejaculation (LPE); and to examine the impact of transitioning from partial to more extensive denervation. A prospective multicenter study including 60 men with LPE unresponsive to optimized medical treatment who underwent MSDP. The primary outcome was to assess changes in Intravaginal Ejaculatory Latency Time (IELT), Premature Ejaculation Profile (PEP), Patients' and Partners' Satisfaction scores at 1, 3, and 6 months after MSDP. The secondary outcome was to evaluate the effect of added-on medical treatment to patients who underwent MSDP without satisfactory results after 6 months. MSDP was associated with statistically significant increases in the mean± SD IELT [from 5.4±0.3 to 77±22, 127±35, and 125±37, p <0.001] and PEP scores [ from 3±0.2 to 9±2.2, 12.1±2.6, and 11.5±1.9, P<0.001] at 1, 3, and 6 months, and 33 (55%) were satisfied. Twenty-seven dissatisfied patients had received added-on medical therapy for 3 months. They showed a statistically significant increase in IELT [from 102±23 to 134±35.6, P <0.001], and PEP scores [from 10.6 ±1.8 to 13 ± 2.3, P=0.002], and 17 (63%) were satisfied. None of the patients developed permanent glans anesthesia, paresthesia, or erectile dysfunction. In selected men with LPE refractory to medical therapy, MSDP, with the protocol and technique modifications presented in the current study, appears to be a safe potential treatment option.
Measurement of the arterial oxygen delivery index (DAO2I) requires substantial medical resources and invasive procedures. We proposed a novel hemodynamic parameter reflecting DAO2I, the Easy DAO2 index (EDI), and examined its association with mortality in non-cardiac surgical and critically ill patients. We retrospectively analyzed the data of 95,115 surgical cases from an Asian hospital and 90,420 intensive care unit (ICU) admissions from multicenter hospitals in the United States. EDI was the product of pulse pressure, heart rate, hemoglobin, and peripheral oxygen saturation, divided by body surface area, measured every 5 minutes during anesthesia and hourly for 24 hours post-ICU admission. We assessed the association between 7-day in-hospital mortality and duration of exposure to EDI values below the fifth percentile levels. In non-cardiac surgical patients, mortality risk increased with duration of exposure below the low EDI threshold (adjusted odds ratio [aOR] 1.003 per minute; 95% CI 1.000-1.005). In critically ill patients, mortality risk increased with duration of exposure below the low EDI threshold (aOR 1.014 per hour; 95% CI 1.004-1.023). Low EDI values were independently associated with mortality in non-cardiac surgical and critically ill patients, suggesting that EDI may be a useful hemodynamic parameter for risk assessment.
Perioperative metabolic vulnerability is an important contributor to postoperative morbidity, yet preoperative risk stratification relies largely on conventional glycemic measures such as hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG). Hemoglobin glycation index (HGI) quantifies interindividual discordance between HbA1c and contemporaneous glycemia and may capture metabolic phenotypes not reflected by absolute glucose values. We investigated the association between preoperative HGI and postoperative outcomes in adults undergoing non-cardiac surgery. We conducted a retrospective single-center cohort study including adult inpatients who underwent non-cardiac surgery under general anesthesia between January 2013 and June 2024. Patients with both preoperative HbA1c and FPG measured within 60 days before surgery were included. HGI was calculated as the residual of observed HbA1c minus HbA1c predicted from FPG using a cohort-specific linear regression model. The primary outcome was any postoperative complication occurring before hospital discharge. Secondary outcomes included major complications (Clavien-Dindo grade ≥ III), organ-specific complications, deep-vein thrombosis, Intensive Care Unit (ICU) admission, hospital and postoperative length of stay, and in-hospital mortality. Associations were evaluated using multivariable regression models with HGI analyzed as a continuous variable (per 1-SD increase) and by quartiles (Q2 as reference), complemented by restricted cubic spline analyses and prespecified subgroup analyses. A total of 24,307 patients were included (mean age 58.8 ± 13.3 years; 51% women). Postoperative complications occurred in 8.4% of patients. In adjusted continuous models, higher HGI was independently associated with postoperative complications (odds ratio [OR] per 1-SD increase 1.068; 95% confidence interval [CI], 1.018-1.120; P = 0.007), urinary complications (OR 1.155; 95% CI, 1.024-1.301; P = 0.018), and longer total hospital length of stay (adjusted mean ratio 1.030; 95% CI, 1.017-1.043; P = 0.001). Quartile analyses demonstrated the lowest risk of postoperative complications in the mid-range HGI group, with higher risks observed at extreme HGI values. Restricted cubic spline models revealed an approximately linear association between HGI and overall postoperative complications, while outcome-specific nonlinear relationships were observed for major complications, ICU admission, and in-hospital mortality. Associations were generally consistent across subgroups, with no statistically significant interaction detected across prespecified strata. Preoperative hemoglobin glycation index was independently associated with postoperative complications after non-cardiac surgery and identified nonlinear risk patterns for selected severe outcomes. HGI may serve as a complementary perioperative metabolic risk marker beyond HbA1c and fasting plasma glucose to provide incremental risk information. The online version contains supplementary material available at 10.1007/s44254-026-00179-w.
Fast-acting botulinum neurotoxins (BoNTs) are highly desirable for both medical and aesthetic indications, but the underlying mechanism for the differing onset of BoNTs' action remains unknown. Here, we demonstrate that the "belt" of BoNTs, a largely unstructured loop wrapping around their catalytic light chain (LC), is key to onset of intoxication. The more flexible BoNT/E belt promotes quicker LC translocation into the neuronal cytosol, leading to faster onset of action compared to BoNT/A. Furthermore, we discover a "belt-buckle" checkpoint that regulates this process. By loosening the BoNT/A belt-buckle via protein engineering, we enhance its sensitivity to acidic pH, leading to an accelerated onset of action. Conversely, locking the belt-buckle with an antibody neutralizes BoNT/A. Our findings open avenues for developing fast-acting BoNTs and effective countermeasures.