Ultrasound-Guided Percutaneous Cryoneurolysis of the Antebrachial Cutaneous Nerves for the Management of Prolonged Acute Post-Surgical Forearm Pain: A Report of Two Cases.

Prolonged acute postsurgical pain (PAPSP) contributes to the development of chronic postsurgical pain, impaired rehabilitation, longer hospital stays, and decreased quality of life. For upper extremity analgesia, the duration of postoperative pain management with continuous brachial plexus peripheral nerve blocks is limited due to the risk of infection. Ultrasound-guided percutaneous cryoneurolysis provides extended analgesia and avoids the risks and inconveniences of indwelling catheters. We present 2 cases of PAPSP of the forearm effectively managed by the use of ultrasound-guided percutaneous cryoneurolysis to treat the medial, lateral, and posterior antebrachial cutaneous nerves.

Characterization and classification of kinesthetic motor imagery levels.

OBJECTIVE: Kinesthetic Motor Imagery (KMI) represents a robust brain paradigm intended for electroencephalography (EEG)-based commands in brain-computer interfaces (BCIs). However, ensuring high accuracy in multi-command execution remains challenging, with data from C3 and C4 electrodes reaching up to 92% accuracy. This paper aims to characterize and classify EEG-based KMI of multilevel muscle contraction without relying on primary motor cortex signals. Approach. A new method based on Hurst exponents is introduced to characterize EEG signals of multilevel KMI of muscle contraction from electrodes placed on the premotor, dorsolateral prefrontal, and inferior parietal cortices. EEG signals were recorded during a hand-grip task at four levels of muscle contraction (0, 10, 40, and 70% of the maximal isometric voluntary contraction). The task was executed under two conditions: first, physically, to train subjects in achieving muscle contraction at each level, followed by mental imagery under the KMI paradigm for each contraction level. EMG signals were recorded in both conditions to correlate muscle contraction execution, whether correct or null accurately. Independent component analysis (ICA) maps EEG signals from the sensor to the source space for preprocessing. For characterization, three algorithms based on Hurst exponents were used: the original (HO), using partitions (HRS), and applying semivariogram (HV). Finally, seven classifiers were used: Bayes network (BN), naive Bayes (NB), support vector machine (SVM), random forest (RF), random tree (RT), multilayer perceptron (MP), and k-nearest neighbours (kNN). Main results. A combination of the three Hurst characterization algorithms produced the highest average accuracy of 96.42% from kNN, followed by MP (92.85%), SVM (92.85%), NB (91.07%), RF (91.07%), BN (91.07%), and RT (80.35%). of 96.42% for kNN. Significance. Results show the feasibility of KMI multilevel muscle contraction detection and, thus, the viability of non-binary EEG-based BCI applications without using signals from the motor cortex.

Tumor-derived hypoxic small extracellular vesicles promote endothelial cell migration and tube formation via ALS2/Rab5/ß-catenin signaling.

Tumor hypoxia has been associated with cancer progression, angiogenesis, and metastasis via modifications in the release and cargo composition of extracellular vesicles secreted by tumor cells. Indeed, hypoxic extracellular vesicles are known to trigger a variety of angiogenic responses via different mechanisms. We recently showed that hypoxia promotes endosomal signaling in tumor cells via HIF-1α-dependent induction of the guanine exchange factor ALS2, which activates Rab5, leading to downstream events involved in cell migration and invasion. Since Rab5-dependent signaling is required for endothelial cell migration and angiogenesis, we explored the possibility that hypoxia promotes the release of small extracellular vesicles containing ALS2, which in turn activate Rab5 in recipient endothelial cells leading to pro-angiogenic properties. In doing so, we found that hypoxia promoted ALS2 expression and incorporation as cargo within small extracellular vesicles, leading to subsequent transfer to recipient endothelial cells and promoting cell migration, tube formation, and downstream Rab5 activation. Consequently, ALS2-containing small extracellular vesicles increased early endosome size and number in recipient endothelial cells, which was followed by subsequent sequestration of components of the ß-catenin destruction complex within endosomal compartments, leading to stabilization and nuclear localization of ß-catenin. These events converged in the expression of ß-catenin target genes involved in angiogenesis. Knockdown of ALS2 in donor tumor cells precluded its incorporation into small extracellular vesicles, preventing Rab5-downstream events and endothelial cell responses, which depended on Rab5 activity and guanine exchange factor activity of ALS2. These findings indicate that vesicular ALS2, secreted in hypoxia, promotes endothelial cell events leading to angiogenesis. Finally, these events might explain how tumor angiogenesis proceeds in hypoxic conditions.

Use of Peripheral Nerve Blocks for Total hip Arthroplasty.

PURPOSE OF REVIEW: The purpose of this review is to summarize the recent literature regarding regional anesthesia (RA) techniques and outcomes for total hip arthroplasty (THA) in the face of changing surgical techniques and perioperative considerations. RECENT FINDINGS: Based on large meta-analyses, peripheral nerve blocks are indicated for THA. Each block has its own risks and benefits and data for outcomes for particular techniques are limited. New surgical techniques, improved use of multimodal analgesia, and improved ultrasound guided regional anesthetics lead to better pain control for patients undergoing THA with less associated risks. Block selection continues to be influenced by provider comfort, surgical approach, patient anatomy, and postoperative goals. Head-to-head studies of particular nerve blocks are warranted.

Effect of Preoperative Bilateral Ultrasound-guided Quadratus Lumborum Nerve Block on Quality of Recovery after Minimally Invasive Hysterectomy in an Enhanced Recovery after Surgery (ERAS) Setting.

STUDY OBJECTIVE: To assess the effect of preoperative bilateral ultrasound-guided quadratus lumborum nerve block (QLB) on quality of recovery after minimally invasive hysterectomy, in an enhanced recovery after surgery setting. DESIGN: Randomized, controlled, double-blinded trial (Canadian Task Force level I). SETTING: University-affiliated tertiary medical center. PATIENTS: All women undergoing an elective robotic or laparoscopic hysterectomy. Women with chronic pain, chronic anticoagulation, and body mass index >50 kg/m2 were excluded. INTERVENTION: Patients were randomized with a 1:1 allocation, to one of the following 2 arms, and stratified based on robotic versus laparoscopic approach. 1. QLB: QLB (bupivacaine) + sham local trocar sites infiltration (normal saline) 2. Local infiltration: sham QLB (normal saline) + local infiltration (bupivacaine) MEASUREMENTS AND MAIN RESULTS: The primary outcome was defined as the quality of recovery score based on the validated questionnaire Quality of Recovery, completed 24 hours postoperatively. Secondary outcomes included dynamic pain scores, accumulated opioid consumption up to 24 hours, postoperative nausea and vomiting, surgical complications, length of hospital stay, time to first pain medication administration in the postanesthesia care unit, and adverse events. A total of 76 women were included in the study. Demographic characteristics were similar in both groups. Median age was 44 years (interquartile range 39-50), 47% of the participants were African American, and mean body mass index was 32.8 kg/m2 (standard deviation [SD] 8.1). The mean Quality of Recovery score was 179.1 (SD ± 10.3) in the QLB and 175.6 (SD ± 9.7) for the local anesthesia group (p = .072). All secondary outcomes were comparable between groups. CONCLUSIONS: QLBs do not significantly improve quality of recovery after elective robotic or laparoscopic hysterectomy compared with local anesthetic port site infiltration.

Glucagon-Like Peptide-1 Receptor Agonist Use and Residual Gastric Content Before Anesthesia.

Importance: Glucagon-like peptide-1 receptor agonist (GLP-1 RA) use is rapidly increasing in the US, driven by its expanded approval for weight management in addition to hyperglycemia management in patients with type 2 diabetes. The perioperative safety of these medications, particularly with aspiration risk under anesthesia, is uncertain. Objective: To assess the association between GLP-1 RA use and prevalence of increased residual gastric content (RGC), a major risk factor for aspiration under anesthesia, using gastric ultrasonography. Design, Setting, and Participants: This cross-sectional study prospectively enrolled patients from a large, tertiary, university-affiliated hospital from June 6 through July 12, 2023. Participants followed preprocedural fasting guidelines before an elective procedure under anesthesia. Patients with altered gastric anatomy (eg, from previous gastric surgery), pregnancy, recent trauma (<1 month), or an inability to lie in the right lateral decubitus position for gastric ultrasonography were excluded. Exposure: Use of a once-weekly GLP-1 RA. Main Outcomes and Measures: The primary outcome was the presence of increased RGC, defined by the presence of solids, thick liquids, or more than 1.5 mL/kg of clear liquids on gastric ultrasonography. Analysis was adjusted for confounders using augmented inverse probability of treatment weighting, a propensity score-based technique. Secondarily, the association between the duration of drug interruption and the prevalence of increased RGC was explored. Results: Among the 124 participants (median age, 56 years [IQR, 46-65 years]; 75 [60%] female), the prevalence of increased RGC was 56% (35 of 62) in patients with GLP-1 RA use (exposure group) compared with 19% (12 of 62) in patients who were not taking a GLP-1 RA drug (control group). After adjustment for confounding, GLP-1 RA use was associated with a 30.5% (95% CI, 9.9%-51.2%) higher prevalence of increased RGC (adjusted prevalence ratio, 2.48; 95% CI, 1.23-4.97). There was no association between the duration of GLP-1 RA interruption and the prevalence of increased RGC (adjusted odds ratio, 0.86; 95% CI, 0.65-1.14). Conclusions and Relevance: Use of a GLP-1 RA was independently associated with increased RGC on preprocedural gastric ultrasonography. The findings suggest that the preprocedural fasting duration suggested by current guidelines may be inadequate in this group of patients at increased risk of aspiration under anesthesia.

Standardizing nomenclature in regional anesthesia: an ASRA-ESRA Delphi consensus study of upper and lower limb nerve blocks.

BACKGROUND: Inconsistent nomenclature and anatomical descriptions of regional anesthetic techniques hinder scientific communication and engender confusion; this in turn has implications for research, education and clinical implementation of regional anesthesia. Having produced standardized nomenclature for abdominal wall, paraspinal and chest wall regional anesthetic techniques, we aimed to similarly do so for upper and lower limb peripheral nerve blocks. METHODS: We performed a three-round Delphi international consensus study to generate standardized names and anatomical descriptions of upper and lower limb regional anesthetic techniques. A long list of names and anatomical description of blocks of upper and lower extremities was produced by the members of the steering committee. Subsequently, two rounds of anonymized voting and commenting were followed by a third virtual round table to secure consensus for items that remained outstanding after the first and second rounds. As with previous methodology, strong consensus was defined as ≥75% agreement and weak consensus as 50%-74% agreement. RESULTS: A total of 94, 91 and 65 collaborators participated in the first, second and third rounds, respectively. We achieved strong consensus for 38 names and 33 anatomical descriptions, and weak consensus for five anatomical descriptions. We agreed on a template for naming peripheral nerve blocks based on the name of the nerve and the anatomical location of the blockade and identified several areas for future research. CONCLUSIONS: We achieved consensus on nomenclature and anatomical descriptions of regional anesthetic techniques for upper and lower limb nerve blocks, and recommend using this framework in clinical and academic practice. This should improve research, teaching and learning of regional anesthesia to eventually improve patient care.

Fibroblast growth factor 21 is expressed and secreted from skeletal muscle following electrical stimulation via extracellular ATP activation of the PI3K/Akt/mTOR signaling pathway.

Fibroblast growth factor 21 (FGF21) is a hormone involved in the regulation of lipid, glucose, and energy metabolism. Although it is released mainly from the liver, in recent years it has been shown that it is a "myokine", synthesized in skeletal muscles after exercise and stress conditions through an Akt-dependent pathway and secreted for mediating autocrine and endocrine roles. To date, the molecular mechanism for the pathophysiological regulation of FGF21 production in skeletal muscle is not totally understood. We have previously demonstrated that muscle membrane depolarization controls gene expression through extracellular ATP (eATP) signaling, by a mechanism defined as "Excitation-Transcription coupling". eATP signaling regulates the expression and secretion of interleukin 6, a well-defined myokine, and activates the Akt/mTOR signaling pathway. This work aimed to study the effect of electrical stimulation in the regulation of both production and secretion of skeletal muscle FGF21, through eATP signaling and PI3K/Akt pathway. Our results show that electrical stimulation increases both mRNA and protein (intracellular and secreted) levels of FGF21, dependent on an extracellular ATP signaling mechanism in skeletal muscle. Using pharmacological inhibitors, we demonstrated that FGF21 production and secretion from muscle requires the activation of the P2YR/PI3K/Akt/mTOR signaling pathway. These results confirm skeletal muscle as a source of FGF21 in physiological conditions and unveil a new molecular mechanism for regulating FGF21 production in this tissue. Our results will allow to identify new molecular targets to understand the regulation of FGF21 both in physiological and pathological conditions, such as exercise, aging, insulin resistance, and Duchenne muscular dystrophy, all characterized by an alteration in both FGF21 levels and ATP signaling components. These data reinforce that eATP signaling is a relevant mechanism for myokine expression in skeletal muscle.

Ultrasound-Guided Percutaneous Intercostal Cryoneurolysis for Acute-on-Chronic Pain in CLOVES Syndrome.

Cryoneurolysis is an analgesic method that has been shown to provide extended pain relief in postoperative patients. However, to date, this method has not been described in nonsurgical inpatients with chronic pain experiencing an acute exacerbation. This analgesic modality has the potential to provide pain relief for patients whose expected duration of severe acute pain would outlast that of other regional anesthetic techniques while avoiding opioid escalation and facilitating discharge. We present a patient with acute exacerbation of chronic pain from breast ulcerations caused by congenital lipomatous overgrowth, vascular malformations, epidermal nevis, spinal/skeletal anomalies/scoliosis (CLOVES) syndrome that was successfully treated as an inpatient with a portable cryoneurolysis device.  This is the first reported use of cryoneurolysis in an inpatient setting to treat acute-on-chronic pain in a nonsurgical patient. The authors recommend regional anesthesiologists and acute pain specialists to utilize this technique to provide analgesia in patients with complex pain to facilitate hospital throughput.

Characterizing the interplay of treatment parameters and complexity and their impact on performance on an IROC IMRT phantom using machine learning.

AIM OF THE STUDY: To elucidate the important factors and their interplay that drive performance on IMRT phantoms from the Imaging and Radiation Oncology Core (IROC). METHODS: IROC's IMRT head and neck phantom contains two targets and an organ at risk. Point and 2D dose are measured by TLDs and film, respectively. 1,542 irradiations between 2012-2020 were retrospectively analyzed based on output parameters, complexity metrics, and treatment parameters. Univariate analysis compared parameters based on pass/fail, and random forest modeling was used to predict output parameters and determine the underlying importance of the variables. RESULTS: The average phantom pass rate was 92% and has not significantly improved over time. The step-and-shoot irradiation technique had significantly lower pass rates that significantly affected other treatment parameters' pass rates. The complexity of plans has significantly increased with time, and all aperture-based complexity metrics (except MCS) were associated with the probability of failure. Random forest-based prediction of failure had an accuracy of 98% on held-out test data not used in model training. While complexity metrics were the most important contributors, the specific metric depended on the set of treatment parameters used during the irradiation. CONCLUSION: With the prevalence of errors in radiotherapy, understanding which parameters affect treatment delivery is vital to improve patient treatment. Complexity metrics were strongly predictive of irradiation failure; however, they are dependent on the specific treatment parameters. In addition, the use of one complexity metric is insufficient to monitor all aspects of the treatment plan.

Assistive artificial intelligence for ultrasound image interpretation in regional anaesthesia: an external validation study.

BACKGROUND: Ultrasonound is used to identify anatomical structures during regional anaesthesia and to guide needle insertion and injection of local anaesthetic. ScanNav Anatomy Peripheral Nerve Block (Intelligent Ultrasound, Cardiff, UK) is an artificial intelligence-based device that produces a colour overlay on real-time B-mode ultrasound to highlight anatomical structures of interest. We evaluated the accuracy of the artificial-intelligence colour overlay and its perceived influence on risk of adverse events or block failure. METHODS: Ultrasound-guided regional anaesthesia experts acquired 720 videos from 40 volunteers (across nine anatomical regions) without using the device. The artificial-intelligence colour overlay was subsequently applied. Three more experts independently reviewed each video (with the original unmodified video) to assess accuracy of the colour overlay in relation to key anatomical structures (true positive/negative and false positive/negative) and the potential for highlighting to modify perceived risk of adverse events (needle trauma to nerves, arteries, pleura, and peritoneum) or block failure. RESULTS: The artificial-intelligence models identified the structure of interest in 93.5% of cases (1519/1624), with a false-negative rate of 3.0% (48/1624) and a false-positive rate of 3.5% (57/1624). Highlighting was judged to reduce the risk of unwanted needle trauma to nerves, arteries, pleura, and peritoneum in 62.9-86.4% of cases (302/480 to 345/400), and to increase the risk in 0.0-1.7% (0/160 to 8/480). Risk of block failure was reported to be reduced in 81.3% of scans (585/720) and to be increased in 1.8% (13/720). CONCLUSIONS: Artificial intelligence-based devices can potentially aid image acquisition and interpretation in ultrasound-guided regional anaesthesia. Further studies are necessary to demonstrate their effectiveness in supporting training and clinical practice. CLINICAL TRIAL REGISTRATION: NCT04906018.

Atypical Response to Affective Touch in Children with Autism: Multi-Parametric Exploration of the Autonomic System.

This study aimed at evaluating the autonomic response to pleasant affective touch in children with Autism Spectrum Disorders (ASD) and age-matched typically developing (TD) peers, thanks to multiple autonomic nervous system (ANS) parameters and by contrasting CT (C-tactile fibers) high- vs. low-density territory stimulations. We measured pupil diameter, skin conductance, and heart rate during gentle stroking of two skin territories (CT high- and low-density, respectively, forearm and palm of the hand) in thirty 6-12-year-old TD children and twenty ASD children. TD children showed an increase in pupil diameter and skin conductance associated with a heart rate deceleration in response to tactile stimulations at the two locations. Only the pupil was influenced by the stimulated location, with a later dilation peak following CT low-density territory stimulation. Globally, ASD children exhibited reduced autonomic responses, as well as different ANS baseline values compared to TD children. These atypical ANS responses to pleasant touch in ASD children were not specific to CT-fiber stimulation. Overall, these results point towards both basal autonomic dysregulation and lower tactile autonomic evoked responses in ASD, possibly reflecting lower arousal and related to social disengagement.

Facial mask disturbs ocular exploration but not pupil reactivity.

Introduction: The COVID-19 pandemic has imposed to wear a face mask that may have negative consequences for social interactions despite its health benefits. A lot of recent studies focused on emotion recognition of masked faces, as the mouth is, with the eyes, essential to convey emotional content. However, none have studied neurobehavioral and neurophysiological markers of masked faces perception, such as ocular exploration and pupil reactivity. The purpose of this eye tracking study was to quantify how wearing a facial accessory, and in particular a face mask, affected the ocular and pupillary response to a face, emotional or not. Methods: We used videos of actors wearing a facial accessory to characterize the visual exploration and pupillary response in several occlusion (no accessory, sunglasses, scarf, and mask) and emotional conditions (neutral, happy, and sad) in a population of 44 adults. Results: We showed that ocular exploration differed for face covered with an accessory, and in particular a mask, compared to the classical visual scanning pattern of a non-covered face. The covered areas of the face were less explored. Pupil reactivity seemed only slightly affected by the mask, while its sensitivity to emotions was observed even in the presence of a facial accessory. Discussion: These results suggest a mixed impact of the mask on attentional capture and physiological adjustment, which does not seem to be reconcilable with its strong effect on behavioral emotional recognition previously described.

COVID-19 masks: A barrier to facial and vocal information.

With the COVID-19 pandemic, we have become used to wearing masks and have experienced how masks seem to impair emotion and speech recognition. While several studies have focused on facial emotion recognition by adding images of masks on photographs of emotional faces, we have created a video database with actors really wearing masks to test its effect in more ecological conditions. After validating the emotions displayed by the actors, we found that surgical mask impaired happiness and sadness recognition but not neutrality. Moreover, for happiness, this effect was specific to the mask and not to covering the lower part of the face, possibly due to a cognitive bias associated with the surgical mask. We also created videos with speech and tested the effect of mask on emotion and speech recognition when displayed in auditory, visual, or audiovisual modalities. In visual and audiovisual modalities, mask impaired happiness and sadness but improved neutrality recognition. Mask impaired the recognition of bilabial syllables regardless of modality. In addition, it altered speech recognition only in the audiovisual modality for participants above 70 years old. Overall, COVID-19 masks mainly impair emotion recognition, except for older participants for whom it also impacts speech recognition, probably because they rely more on visual information to compensate age-related hearing loss.

Autonomic tone in children and adults: Pupillary, electrodermal and cardiac activity at rest.

Considering the suspected involvement of the autonomic nervous system (ANS) in several neurodevelopmental disorders, a description of its tonus in typical populations and of its maturation between childhood and adulthood is necessary. We aimed to arrive at a better understanding of the maturation of the sympathetic (SNS) and parasympathetic (PNS) tonus by comparing children and adults at rest, via recordings of multiple ANS indices. We recorded simultaneously pupil diameter, electrodermal activity (EDA) and cardiac activity (RR interval and HRV: heart rate variability) in 29 children (6-12 years old) and 30 adults (20-42 years old) during a 5-min rest period. Children exhibited lower RR intervals, higher LF peak frequencies, and lower LF/HF (low frequency/high frequency) ratios compared to adults. Children also produced more spontaneous EDA peaks, reflected in a larger EDA AUC (area under the curve), in comparison with adults. Finally, children displayed a larger median pupil diameter and a higher pupillary hippus frequency than adults. Our results converged towards higher SNS and PNS tones in children compared to adults. Childhood would thus be characterized by a high autonomic tone, possibly reflecting a physiological state compatible with developmental acquisitions.

Mechanical Disturbance of Osteoclasts Induces ATP Release That Leads to Protein Synthesis in Skeletal Muscle through an Akt-mTOR Signaling Pathway.

Muscle and bone are tightly integrated through mechanical and biochemical signals. Osteoclasts are cells mostly related to pathological bone loss; however, they also start physiological bone remodeling. Therefore, osteoclast signals released during bone remodeling could improve both bone and skeletal muscle mass. Extracellular ATP is an autocrine/paracrine signaling molecule released by bone and muscle cells. Then, in the present work, it was hypothesized that ATP is a paracrine mediator released by osteoclasts and leads to skeletal muscle protein synthesis. RAW264.7-derived osteoclasts were co-cultured in Transwell® chambers with flexor digitorum brevis (FDB) muscle isolated from adult BalbC mice. The osteoclasts at the upper chamber were mechanically stimulated by controlled culture medium perturbation, resulting in a two-fold increase in protein synthesis in FDB muscle at the lower chamber. Osteoclasts released ATP to the extracellular medium in response to mechanical stimulation, proportional to the magnitude of the stimulus and partly dependent on the P2X7 receptor. On the other hand, exogenous ATP promoted Akt phosphorylation (S473) in isolated FDB muscle in a time- and concentration-dependent manner. ATP also induced phosphorylation of proteins downstream Akt: mTOR (S2448), p70S6K (T389) and 4E-BP1 (T37/46). Exogenous ATP increased the protein synthesis rate in FDB muscle 2.2-fold; this effect was blocked by Suramin (general P2X/P2Y antagonist), LY294002 (phosphatidylinositol 3 kinase inhibitor) and Rapamycin (mTOR inhibitor). These blockers, as well as apyrase (ATP metabolizing enzyme), also abolished the induction of FDB protein synthesis evoked by mechanical stimulation of osteoclasts in the co-culture model. Therefore, the present findings suggest that mechanically stimulated osteoclasts release ATP, leading to protein synthesis in isolated FDB muscle, by activating the P2-PI3K-Akt-mTOR pathway. These results open a new area for research and clinical interest in bone-to-muscle crosstalk in adaptive processes related to muscle use/disuse or in musculoskeletal pathologies.