Search Results (138)

Risdiplam is the first approved small-molecule therapy for spinal muscular atrophy (SMA), a severe, progressive neuromuscular disorder. In addition to its clinical significance, risdiplam is of a great interest for organic and medicinal chemistry due to its complex molecular architecture. Its structure incorporates three highly substituted heterocyclic fragments—imidazo[1,2-b]pyridazine, pyrido[1,2-a]pyrimidin-4-one, and 4,7-diazaspiro[2.5]octane—that serve as both versatile synthetic building blocks and critical pharmacophoric elements for drug design and discovery. The increasing scientific interest in risdiplam has led to numerous publications and patent applications that describe alternative synthetic methodologies. Recently, our group has also developed and introduced efficient, scalable manufacturing routes for the preparation of the target substance and the key intermediates of its synthesis. This mini-review systematically analyzes a plethora of risdiplam assembly strategies and synthetic approaches, covering developments from 2013 to the present. Full article

Background/Objectives: The aim of this observational study was to collect hand measurements and anthropometric data in children aged 1–15 years of age to help the design of a pediatric skin electrode for electromyography-based neuromuscular monitoring. Methods: Data collection was performed at the Pediatric Department of the University of Debrecen Medical Centre between 1 December 2019 and 31 January 2021. After gaining written informed consent from the parents or legal representatives and verbal acceptance from age-appropriate (12–35 months) patients, a total of 153 children were enrolled. The following parameters were recorded: demographics (age, sex, weight, height, and hand dominance) and hand size parameters, defined as the distance between the following reference points: the ulnar groove and the midpoint of the hypothenar eminence (A); the midpoint of the hypothenar eminence and the first interphalangeal joint of the 5th finger (B); the ulnar groove and the midpoint of the thenar eminence (C); the midpoint of the thenar eminence and the interphalangeal joint of the thumb (D); the midpoint of the wrist crease and the tip of the third finger; wrist circumference (E); and forearm length. All measurements were made in centimeters (cm). Results: The children were divided into 4 groups (12–23 months, 2–5 years, 6–11 years and 12+ years). The number of children in the groups ranged between 6 and 16. The hand size parameters increased according to the children’s age (A: 4.3 ± 0.4, 5.0 ± 0.7, 6.3 ± 0.6, and 6.9 ± 1.0 cm; B: 3.2 ± 0.4, 4.1 ± 0.7, 5.0 ± 0.6, and 5.9 ± 0.6 cm; C: 3.0 ± 0.3, 3.6 ± 0.7, 4.1 ± 0.6, and 4.9 ± 0.6 cm; D: 4.1 ± 0.4, 4.8 ± 0.8, 6.2 ± 0.8, and 7.2 ± 0.9 cm; E: 10.1 ± 0.6, 12.0 ± 1.1, 15.3 ± 1.3, and 17.7 ± 1.7 cm, respectively, in the four groups, [mean ± SD]). The height of the children showed a closer correlation with hand size parameters (Pearson’s correlation coefficients: 0.702–0.961) than with age (0.665–0.904) or weight (0.675–0.863). The correlation was weaker when data were examined in prespecified age groups. Conclusions: The current pediatric hand size database provides previously unavailable information that was used in one manufacturer’s design, which may help with the future design of pediatric electrodes of electromyography-based neuromuscular monitors; this information may facilitate adoption of quantitative neuromuscular monitoring in routine pediatric anesthesia practice. Full article

Background: Conventional rehabilitation after anterior cruciate ligament reconstruction often follows a rigid, phase-based model. This structure may overlook individual differences in healing, neuromuscular control, and psychological readiness, leading to low return-to-sport rates and a high risk of reinjury. Methods: This narrative review proposes a flexible rehabilitation framework based on overlapping progression blocks. Inspired by principles of strength and conditioning, motor learning, and cognitive training, this model emphasizes continuous, individualized development instead of fixed timelines. Results: The proposed model integrates essential components—such as joint mobility, muscle activation, motor control, and psychological factors—throughout the entire recovery process. Functional testing is redefined as a dynamic and ongoing diagnostic tool that helps clinicians identify areas needing further development, rather than acting as a simple pass/fail gateway. Progression is guided by demonstrated readiness rather than time or phase completion. Conclusions: Rehabilitation using adaptive, overlapping progression blocks offers a more holistic and responsive approach. It allows for better personalization, supports safer decision-making, and improves the transition back to sport through sustained development of physical and cognitive capacities. Full article

Neuromuscular blocking agents (NMBAs) are essential in intraocular surgeries to improve surgical conditions and ensure optimal ventilation. However, residual blockade can pose significant risks, particularly in pinnipeds due to their unique diving physiology. This case report describes the use of sugammadex for reversing rocuronium and AMG for monitoring neuromuscular block (NMB) in a California sea lion undergoing lensectomy. The objective is to evaluate the feasibility and safety of sugammadex for reversal of rocuronium-induced neuromuscular blockade and acceleromyography (AMG) for monitoring neuromuscular function in pinnipeds, with the goal of improving anesthetic management and recovery. Rocuronium (0.3 mg/kg IV) was used to achieve complete NMB, and an additional 0.1 mg/kg IV was administered to prolong the block. Sugammadex (1 mg/kg IV) reversed the NMB, with recovery within 90 s. Neuromuscular function was monitored using AMG, with the ulnar nerve of the foreflipper as the stimulation site. AMG allowed for an objective assessment of neuromuscular function, ensuring accurate titration of the NMBA and reversal agent. This is the first report documenting the use of sugammadex for the reversal of rocuronium and AMG for neuromuscular monitoring in a sea lion. This successful application highlights the potential of these techniques to improve anesthesia protocols, patient safety, and welfare in marine mammal medicine. Full article

Background: There is little data available in infants on the extent to which inhalational anesthetics prolong the effects of neuromuscular blocking agents compared with intravenous agents. Here, we assessed the differences between the neuromuscular blocking effects (duration and recovery time) of a single dose of rocuronium during propofol vs. sevoflurane anesthesia. Methods: The prospective study enrolled 20 infants (4–12 months of age) scheduled for craniosynostosis surgery, randomly assigned to receive general anesthesia maintenance with sevoflurane or propofol. All patients received 0.6 mg/kg rocuronium as a single bolus dose to facilitate tracheal intubation and surgery. Primary study endpoint was the clinical duration of rocuronium, from administration until spontaneous recovery to a train-of-four ratio (TOFR) > 0.90. Secondary endpoints were times for reappearance of the first, second, third, and fourth twitches of the TOF (T1, T2, T3 and T4, respectively) in the two patient groups. Results: There were no differences in the infants’ age (sevoflurane maintenance: 5.8 ± 2.4 months; propofol maintenance: 6.7 ± 3.1 months, p = 0.47) or weight (sevoflurane: 7722 ± 1644 g; propofol: 7433 ± 1782 g, p = 0.71). Rocuronium onset time was 101.0 ± 55.0 s in the sevoflurane group and 83.4 ± 47.9 s in the propofol group (p = 0.46). Total duration of anesthesia was comparable in the sevoflurane (122.0 ± 23.8 min) and propofol (107.7 ± 25.2 min, p = 0.18) groups. Rocuronium recovery to TOFR > 0.9 required 136 min (CI: 123.7–149.5 min) in the sevoflurane group and 61.5 min (CI: 58.0–101.0 min) in the propofol group (p < 0.001). Conclusions: In infants, sevoflurane maintenance enhances the neuromuscular blocking effect of a single, 0.6 mg/kg BW dose of rocuronium as compared to propofol maintenance. After discontinuation of sevoflurane, additional time is necessary to reach the acceptable TOFR >0.9 needed before tracheal extubation. The present study further underscores the importance of objective (quantitative) neuromuscular monitoring in infants to guide intraoperative management and prevent residual neuromuscular block. Full article

Background/Objectives: Current guidelines recommend objective neuromuscular monitoring to ensure patient safety during neuromuscular blockade. Acceleromyography using train-of-four (TOF) stimulation is most commonly used to assess neuromuscular function. This study compares a new electromyography-based monitor with an established acceleromyography device for neuromuscular monitoring when mounted on a restricted arm. Methods: This prospective, controlled observational study enrolled patients undergoing surgery with general anesthesia requiring neuromuscular blockade. Two neuromuscular monitoring systems were used simultaneously: the standard acceleromyography device (Philips IntelliVue MX550) and the electromyography-based TetraGraph^® monitor on the opposite arm. Atracurium was administered as the neuromuscular blocking agent. The TetraGraph^® arm was restricted during surgery. The primary outcome was the time for the TOF ratio to return to ≥90%. Secondary endpoints included the time to reach a TOF count of 0 during induction. Data were analyzed using Bland–Altman plots and a paired t-test. Results: Mean time to recovery to TOF ratio ≥ 90% was 67 min (±21.4) for IntelliVue MX 550 and 75.8 min (±22.3) for TetraGraph^® (p = 0.0001; mean bias 8.9 min, 95% confidence intervals (CIs) 5.99–11.8). The mean time to reach a TOF count of 0 was 180.6 s (±7.8) for IntelliVue and 200 s (±8.2) for TetraGraph^® (p = 0.0217; mean bias 19 s, 95% CI 2.96–35.8). Conclusions: TetraGraph^® consistently recorded the endpoints later than IntelliVue, reflecting slower onset and recovery times. However, substantial intra-individual variability was observed with both devices during recovery from neuromuscular block. The observed differences may have clinical implications, such as when assessing readiness for extubation. Full article

Background and Objectives: Obturator reflex during transurethral resection of bladder tumors (TURBT) can cause serious complications, such as bladder perforation, hemorrhage, and incomplete resection. Although obturator nerve block (ONB) is routinely recommended under spinal anesthesia, it is often omitted under general anesthesia (GA) based on the assumption that neuromuscular blockade (NMB) alone prevents adductor muscle contractions. However, clinical observations suggest that the obturator reflex may still occur under deep NMB. This study aimed to determine whether adductor longus muscle (ALM) contraction persists under GA with deep NMB during TURBT. Materials and Methods: Thirty patients scheduled for TURBT under GA were prospectively enrolled. A selective ONB was performed under ultrasound and nerve stimulator guidance. After establishing the baseline current intensity for ALM contraction, neuromuscular monitoring was initiated, and rocuronium (0.6 mg/kg) was administered. Stimulation thresholds required to induce ALM contraction were sequentially assessed at decreasing Train-of-Four ratio (TOFr) stages (90% to 10%) and Train-of-Four count (TOFc) stages (3 to 0). Final measurements were repeated 1 min after achieving TOFc 0. Changes in stimulation intensity were analyzed using a linear mixed-effects model (LMM). Results: As NMB deepened, the current intensity required to provoke ALM contraction progressively increased: 0.51 ± 0.25 mA at TOFr 90%, 1.66 ± 0.53 mA at TOFr 10%, 2.04 ± 0.66 mA at TOFc 0, and 2.61 ± 0.29 mA at 1 min after TOFc 0. Notably, all patients demonstrated ALM contraction at TOFc 0 and thereafter, confirming the persistence of the obturator reflex despite complete NMB. LMM analysis revealed a significant trend of increasing stimulation thresholds with progressive NMB depth (β = 0.133, p < 0.001). Conclusions: Adductor muscle contractions in response to obturator nerve stimulation persist even under deep NMB. These findings raise concerns that deep NMB alone may be insufficient to prevent obturator reflex and suggest that ONB should be considered as an adjunctive practice during TURBT under GA in patients at risk. Full article

Neuromuscular blocking agents such as atracurium and rocuronium are commonly used during anesthetic procedures in laboratory pigs. However, species-specific dosing guidelines remain limited, leading to reliance on data extrapolated from other species. This prospective, blinded study aimed to determine the equipotent dose for atracurium (A) and rocuronium (R) in laboratory pigs receiving propofol and to compare their cost-effectiveness. Twelve healthy animals were randomly distributed according to the drug administered (n = 6 per group). For both drugs, the infusion rate was adjusted following an up-and-down titration to maintain a train-of-four count between 3 and 4. Group differences were analyzed using the Wilcoxon signed-rank test. The bolus induction dose (mg/kg) was comparable between atracurium (2.3 [1.8–2.6]) and rocuronium (2 [2]), while atracurium was associated with higher costs (CHF/kg: A, 1.122 [0.878–1.366] versus R, 0.208 [0.208–0.208]; p = 0.002725). The maintenance infusion rate (mg/kg/h) was approximately 40% lower for atracurium (2.7 [2.5–2.8]) than for rocuronium (4.5 [4.4–4.5]; p = 0.004922), yet the maintenance cost (CFH/kg/h) remained higher for atracurium (A: 1.30 [1.22–1.37] versus R: 0.47 [0.45–0.47]; p = 0.0043). This study reports higher doses for anesthetized pigs compared to other species and demonstrates that rocuronium offers superior cost-effectiveness compared to atracurium under these experimental conditions. Full article

Background: Tracheal intubation and mechanical ventilation are facilitated by neuromuscular blocking agents. We investigated the effectiveness of subjective clinical evaluation of neuromuscular function on retroglossal area size, since it determines spontaneous ventilation adequacy following tracheal extubation. Secondarily, we correlated changes in retroglossal area and depth of neuromuscular block assessed during both respiratory phases using quantitative neuromuscular monitoring. Methods: Once mechanical ventilation was no longer needed, antagonists were used to reverse the neuromuscular block in 21 consenting patients; adequacy of reversal was assessed subjectively by delivering a sequence of four rapid (2 Hz) electrical stimuli (train-of-four, TOF) to a peripheral nerve and assessing attainment of four equal muscle contractions (TOF ratio = 1.0), signifying normal neuromuscular function. Retroglossal area during both inhalation and exhalation were measured pharyngoscopically at various phases of neuromuscular recovery, including at baseline after anesthesia induction but before neuromuscular block onset and at recovery before tracheal extubation; area changes were correlated with depth of quantitatively measured neuromuscular block. Results: Clinicians’ subjective evaluation of readiness for tracheal extubation failed to identify significant residual block in most patients who required rescue antagonism. Markedly decreased retroglossal areas (inhalation: 39.5% of baseline; exhalation: 20.1% of baseline) were present at extubation, and 11 out of 21 (52.4%) patients needed rescue antagonism. In contrast, in patients with neuromuscular recovery to the currently recommended threshold determined quantitatively (TOF ratio > 0.90), retroglossal areas were only 80% recovered but returned to near baseline values when the TOF ratio ≥ 0.95. Conclusions: Quantitative monitoring should guide the timing of tracheal extubation. Current definitions of the minimal threshold for adequate neuromuscular recovery (TOF ratio > 0.90) after mechanical ventilation in postoperative patients should be re-evaluated. A TOF ratio > 0.95 better correlates with return to normal (baseline) retroglossal area during both inhalation and exhalation. Full article

This study examined the use of linear regression models for predicting the outcomes of a six-week velocity-based training (VBT) intervention in female floorball players. The intervention was integrated into regular training and consisted of brief 30-min sessions focused on back squats and trap bar deadlifts. Key performance metrics included neuromuscular adaptation, sprint speed, jump performance, stop-and-go (SAG) performance, and load-velocity profiles. Seventeen participants completed 12 training sessions, a strength block set (Sessions 1–6) and a power block set (Sessions 7–12). The predictive models explained 54% to 79% ($R^2$ = 0.54–0.79) of the performance improvement in the strength-related tests. Significant gains were observed in neuromuscular metrics, including estimated one-repetition maximum (1${\mathrm{RM}}_{est}$) and average mean concentric velocity for both exercises. These findings underscore the predictive potential of VBT in enhancing strength and power while highlighting the need to integrate task-specific exercises to optimize sport-specific performance. This study provides valuable insights for tailoring VBT strategies for female athletes in high-demand team sports such as floorball. Full article

Objectives: Interval block resistance training (IBRT) and circuit resistance training (CRT) are periodization models aimed at enhancing neuromuscular and metabolic adaptations. This study aims to evaluate the effects of a 12-week IBRT program compared to CRT on body composition, muscle strength, speed, functional capacity, and autonomic recovery in young Chilean adults. Methods: A randomized, parallel, double-blind study was conducted with 30 participants assigned to IBRT (n = 15) or CRT (n = 15). Assessments included body mass index (BMI), waist circumference, right-hand grip strength, the running anaerobic sprint test (RAST), the 6 min walk test (6 MWT), and heart rate variability (HRV) indices: low-frequency to high-frequency ratio (LF/HF) and root mean square of successive differences (RMSSD, a time-domain HRV metric reflecting parasympathetic activity). Statistical analyses included t-tests and ANCOVA. Results: Groups were similar in age (IBRT: 25.2 ± 3.19; CRT: 23.27 ± 3.69, p = 0.14) and BMI (IBRT: 21.56 ± 2.22; CRT: 22.36 ± 1.70 kg/m², p = 0.40). Both groups improved significantly in waist circumference (IBRT: −1.85%; CRT: −2.37%), grip strength (IBRT: +5.47%; CRT: +4.02%), RAST (IBRT: −2.67%; CRT: −1.04%), 6 MWT (IBRT: +4.53%; CRT: +2.17%), LF/HF (IBRT: −11.43%; CRT: −5.11%), and RMSSD (IBRT: +5.36%; CRT: +3.81%) (all p ≤ 0.01). IBRT produced significantly greater gains in 6 MWT (B = 19.51, 95% CI: 0.79 to 38.23, p = 0.04). Conclusions: Both IBRT and CRT effectively improved body composition, muscle strength, speed, functional capacity, and autonomic recovery. However, IBRT demonstrated a superior effect on aerobic capacity. Full article

(1) Background: The aim of this bibliometric study is to analyze global research trends, citation impact, and scientific collaborations in the field of neuromuscular blockers (NMBAs) and their antagonists between 2000 and 2024. (2) Methods: Data were retrieved from the Web of Science Core Collection (WoSCC) using Boolean search strategies. Bibliometric analyses were conducted using R bibliometrix, VOSviewer, and CiteSpace software to visualize collaboration networks, keyword trends, and citation bursts. (3) Results: A total of 499 articles were analyzed, with the United States of America (USA), China, and South Korea leading in productivity, while France had the highest citation impact. Influential authors included Mertes PM and Fuchs-Buder T. Emerging topics such as sugammadex, sevoflurane, and neuromuscular monitoring were identified, reflecting a shift from pharmacokinetic studies to safety and monitoring strategies. (4) Conclusions: The findings indicate a marked increase in studies on neuromuscular monitoring and reversal agents, such as sugammadex, over the past two decades. The USA, France, and China emerged as the most contributory countries in NMBAs research, with their extensive international collaborations playing a pivotal role in shaping scientific progress. Highly influential studies have predominantly focused on NMBA pharmacokinetics, safety, anaphylaxis risks, and the clinical benefits of sugammadex, underscoring its critical role in reducing residual neuromuscular blockade (rNMB) and enhancing patient safety. Full article

Background: Intraoperative nerve monitoring (IONM) is increasingly recognized as an essential technique in thyroid surgery to preserve the integrity of the recurrent laryngeal nerve (RLN) and prevent postoperative complications. Although widely adopted, several technical and anesthetic factors can significantly affect the reliability and interpretation of electromyographic (EMG) signals. Methods: This narrative review summarizes the principles and methodologies of IONM in thyroid surgery, focusing on the mechanisms of RLN injury, the clinical benefits of IONM, and its limitations. Particular emphasis is placed on the anesthesiologic considerations, including the effects of neuromuscular blocking agents and anesthetic maintenance methods for EMG signal quality. Recent advances in alternative IONM techniques are also discussed. Results: IONM facilitates early detection of RLN injury and improves surgical outcomes. However, signal loss and technical errors occur in up to 23% of cases. Appropriate anesthetic management, such as the judicious use of neuromuscular blocking agents and the use of reversal agents like sugammadex, can significantly improve IONM accuracy. Alternative approaches, such as transcutaneous or thyroid cartilage electrode-based monitoring, show promise in overcoming current limitations. Conclusions: IONM is a valuable tool in modern thyroid surgery, aiding in the prevention of RLN injury. Anesthesiologists play a crucial role in optimizing IONM quality by managing factors that affect EMG signals. Ongoing research into novel monitoring techniques is expected to further enhance patient safety and surgical precision. Full article

This Critical Appraisal aims to explore the pharmacokinetics and pharmacodynamics of medications used in organ donors after euthanasia (ODE) and their impact on abdominal organ quality. With the legalization of ODE, the donor pool has expanded, but it has introduced complexities regarding organ quality. This study evaluates existing euthanasia protocols in the Netherlands, Belgium, Spain, and Canada, focusing on differences in the medication types and dosages. Additionally, a literature review assessed the potential hepatotoxic effects of high-dose medications like thiopental, propofol, and non-depolarizing neuromuscular blocking agents. High doses of non-depolarizing neuromuscular blocking agents, particularly rocuronium, are associated with hepatotoxic effects in vitro. Furthermore, thiopental doses exceeding 750 mg significantly increase the risk of liver dysfunction. Recent findings also indicate that high-dose propofol and lidocaine can slightly prolong the time to death, which is crucial for optimizing organ viability in ODE. This study highlights the need to optimize organ donation procedures after euthanasia. Further research is needed to achieve this balance, maintaining the integrity and ethical standards of the euthanasia process while enhancing the outcomes of organ donation. Full article

Myofascial pain syndrome (MPS) is a common musculoskeletal disorder that significantly affects quality of life. Conventional treatment approaches include pharmacological interventions, physical therapy, and procedures such as dry needling. Among these, ultrasound-guided injections (USGIs) have gained recognition for their precision and therapeutic benefits. Additionally, repetitive peripheral magnetic stimulation (rPMS) has emerged as a non-invasive neuromodulatory technique for pain management. This perspective article examines the physiological mechanisms and clinical applications of USGIs and rPMS, particularly in the lumbar multifidus muscle, and explores their potential synergistic effects. MPS is often associated with chronic muscle dysfunction due to energy depletion, leading to persistent pain and motor impairment. USGIs play a crucial role in restoring muscle perfusion, disrupting pain cycles, and providing diagnostic insights in real time. In parallel, rPMS modulates neuromuscular activation, enhances endogenous pain control, and promotes functional recovery. Ultrasound guidance enhances the precision and effectiveness of interventions, such as dry needling, interfascial plane blocks, and fascial hydrodissection, while rPMS complements these strategies by facilitating neuromuscular reconditioning and reducing pain via central and peripheral mechanisms. The preliminary findings suggest that combining multifidus USGIs with rPMS results in significant pain relief and functional improvements in patients with chronic low back pain. Integrating USGIs with rPMS represents a promising multimodal strategy for managing MPS. By combining targeted injections with non-invasive neuromodulation, clinicians may optimize therapeutic outcomes and provide sustained relief for patients with chronic musculoskeletal pain. Further research is needed to refine treatment protocols and assess the long-term efficacy. Full article