Investigation into the clinical performance of rectus sheath block in reducing postoperative pain following surgical intervention: A systematic review and meta-analysis of randomised controlled trials.

Background and Aims: Rectus sheath block (RSB) is an effective postoperative pain control technique in abdominal surgical procedures. This systematic review evaluated the efficacy and outcome data of patients undergoing RSB compared to the standard of care in both laparoscopic and open surgical procedures. Methods: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO ID: CRD42022372596). The search was restricted to randomised controlled trials (RCTs) comparing RSB effectiveness on postoperative pain to any standard general anaesthesia technique (control). We systematically explored PubMed, Medline, Central, Scopus and Web of Science for RCTs from inception to September 2023. The primary outcome was the evaluation of pain scores at rest 0-2, 10-12 and 12-24 h postoperatively. The secondary outcome was the analysis of postoperative intravenous (IV) morphine equivalent consumption at 24-h. A risk-of-bias tool for randomised trials (ROB 2.0, Cochrane, Copenhagen, Denmark) assessment and Grades of Recommendation, Assessment, Development and Evaluation (GRADE, Cochrane, Copenhagen, Denmark) analysis was conducted to evaluate the quality of the RCTs. Results: Twenty RCTs involving 708 participants who received RSB intervention and 713 who received alternative analgesic care were included. RSB pain scores were significantly lower than control at 0-2 h (P < 0.001) and 10-12 h (P < 0.001) postoperatively. No significant effect was observed at 24 h (P = 0.11). RSB performance compared to control in 24-h IV morphine equivalency in milligrams was significantly lower (P < 0.001). Conclusion: RSB implementation was associated with reduced postoperative pain scores and decreased opioid consumption in IV morphine equivalency up to 24 h following surgical intervention.

Beyond the Echo: The Evolution and Revolution of Ultrasound in Anesthesia.

This article explores the evolving role of ultrasound technology in anesthesia. Ultrasound emerged decades ago, offering clinicians noninvasive, economical, radiation-free, and real-time imaging capabilities. It might seem that such an old technology with apparent limitations might have had its day, but this review discusses both the current applications of ultrasound (in nerve blocks, vascular access, and airway management) and then, more speculatively, shows how integration of advanced ultrasound modalities such as contrast-enhanced imaging with virtual reality (VR), or nanotechnology can alter perioperative patient care. This article will also explore the potential of robotics and artificial intelligence (AI) in augmenting ultrasound-guided anesthetic procedures and their implications for medical practice and education.

Fc gamma receptors promote antibody-induced LILRB4 internalization and immune regulation of monocytic AML.

The immune checkpoint leukocyte immunoglobulin-like receptor B4 (LILRB4) is found specifically on the cell surface of acute monocytic leukemia (monocytic AML), an aggressive and common subtype of AML. We have developed a humanized monoclonal IgG1 LILRB4-blocking antibody (h128-3), which improved immune regulation but reduced cell surface expression of LILRB4 in monocytic AML models by 40-60%. Interestingly, most of this effect was neutralized by mutation of the Fc region of the antibody (h128-3/N297A), which prevents interaction with Fc gamma receptors (FcγRs). This suggested that there is FcγR-dependent antigenic modulation underlying h128-3's effects, a mechanism known to alter the function of antibodies targeting B-cell malignancies. We disrupted the Fc-FcγR interaction pharmacologically and with stable CRISPR-Cas9-mediated genetic knockout of FcγRs in monocytic AML cell lines to investigate the role of FcγR-dependent antigenic modulation in the regulation of LILRB4 by h128-3. When FcγRI is inhibited or removed from the surface of monocytic AML cells, h128-3 cannot optimally perform its blocking function, resulting in activation of the LILRB4 inhibitory receptor and leading to a 15-25% decrease in T-cell-mediated cytotoxicity in vitro. In the absence of FcγRI, scaffolding by FcγRIIa allows h128-3 to maintain LILRB4-blocking function. Here we define a FcγR-dependent antigenic modulation mechanism underlying the function of an immunoreceptor blocking antibody for the first time in myeloid malignancy. This research will facilitate the development of safe, precision-targeted antibody therapeutics in myeloid malignancies with greater potency and efficacy.

Antibody therapies for the treatment of acute myeloid leukemia: exploring current and emerging therapeutic targets.

INTRODUCTION: Acute myeloid leukemia (AML) is the most common and deadly type of leukemia affecting adults. It is typically managed with rounds of non-targeted chemotherapy followed by hematopoietic stem cell transplants, but this is only possible in patients who can tolerate these harsh treatments and many are elderly and frail. With the identification of novel tumor-specific cell surface receptors, there is great conviction that targeted antibody therapies will soon become available for these patients. AREAS COVERED: In this review, we describe the current landscape of known target receptors for monospecific and bispecific antibody-based therapeutics for AML. Here, we characterize each of the receptors and targeted antibody-based therapeutics in development, illustrating the rational design behind each therapeutic compound. We then discuss the bispecific antibodies in development and how they improve immune surveillance of AML. For each therapeutic, we also summarize the available pre-clinical and clinical data, including data from discontinued trials. EXPERT OPINION: One antibody-based therapeutic has already been approved for AML treatment, the CD33-targeting antibody-drug conjugate, gemtuzumab ozogamicin. Many more are currently in pre-clinical and clinical studies. These antibody-based therapeutics can perform tumor-specific, elaborate cytotoxic functions and there is growing confidence they will soon lead to personalized, safe AML treatment options that induce durable remissions.

COVID-19 and human-nature relationships: Vermonters' activities in nature and associated nonmaterial values during the pandemic.

The COVID-19 pandemic has rapidly modified Earth's social-ecological systems in many ways; here we study its impacts on human-nature interactions. We conducted an online survey focused on peoples' relationships with the non-human world during the pandemic and received valid responses from 3,204 adult residents of the state of Vermont (U.S.A.). We analyzed reported changes in outdoor activities and the values associated with human-nature relationships across geographic areas and demographic characteristics. We find that participation increased on average for some activities (foraging, gardening, hiking, jogging, photography and other art, relaxing alone, walking, and watching wildlife), and decreased for others (camping, relaxing with others). The values respondents ranked as more important during the pandemic factored into two groups, which we label as "Nurture and Recreation values" and "Inspiration and Nourishment values." Using multinomial logistic regression, we found that respondents' preferences for changes in activity engagement and value factors are statistically associated with some demographic characteristics, including geography, gender, income, and employment status during the pandemic. Our results suggest that nature may play an important role in coping during times of crisis, but that the specific interactions and associated values that people perceive as most important may vary between populations. Our findings emphasize for both emergency and natural resources planning the importance of understanding variation in how and why people interact with and benefit from nature during crises.

Biological and metabolic effects of IACS-010759, an OxPhos inhibitor, on chronic lymphocytic leukemia cells.

Blood cells from patients with chronic lymphocytic leukemia (CLL) are replicationally quiescent but transcriptionally, translationally, and metabolically active. Recently, we demonstrated that oxidative phosphorylation (OxPhos) is a predominant pathway in CLL for energy production and is further augmented in the presence of the stromal microenvironment. Importantly, CLL cells from patients with poor prognostic markers showed increased OxPhos. From these data, we theorized that OxPhos can be targeted to treat CLL. IACS-010759, currently in clinical development, is a small-molecule, orally bioavailable OxPhos inhibitor that targets mitochondrial complex I. Treatment of primary CLL cells with IACS-010759 greatly inhibited OxPhos but caused only minor cell death at 24 and 48 h. In the presence of stroma, the drug successfully inhibited OxPhos and diminished intracellular ribonucleotide pools. However, glycolysis and glucose uptake were induced as compensatory mechanisms. To mitigate the upregulated glycolytic flux, we used 2-deoxy-D-glucose in combination with IACS-010759. This combination reduced both OxPhos and glycolysis and induced cell death. Consistent with these data, low-glucose culture conditions sensitized CLL cells to IACS-010759. Collectively, these data suggest that CLL cells adapt to use a different metabolic pathway when OxPhos is inhibited and that targeting both OxPhos and glycolysis pathways is necessary for biological effect.

Targeting Stromal Glutamine Synthetase in Tumors Disrupts Tumor Microenvironment-Regulated Cancer Cell Growth.

Reactive stromal cells are an integral part of tumor microenvironment (TME) and interact with cancer cells to regulate their growth. Although targeting stromal cells could be a viable therapy to regulate the communication between TME and cancer cells, identification of stromal targets that make cancer cells vulnerable has remained challenging and elusive. Here, we identify a previously unrecognized mechanism whereby metabolism of reactive stromal cells is reprogrammed through an upregulated glutamine anabolic pathway. This dysfunctional stromal metabolism confers atypical metabolic flexibility and adaptive mechanisms in stromal cells, allowing them to harness carbon and nitrogen from noncanonical sources to synthesize glutamine in nutrient-deprived conditions existing in TME. Using an orthotopic mouse model for ovarian carcinoma, we find that co-targeting glutamine synthetase in stroma and glutaminase in cancer cells reduces tumor weight, nodules, and metastasis. We present a synthetic lethal approach to target tumor stroma and cancer cells simultaneously for desirable therapeutic outcomes.

Polymyxin B Direct Hemoperfusion Using Regional Citrate-Calcium Anticoagulation: A Case Report.

Direct hemoperfusion with polymyxin B (PMX-DHP) is an extracorporeal treatment to add to conventional therapy during unresponsive endotoxic septic shock. So far, only heparin has been used as an anticoagulant during polymyxin B therapy. We present a case report of a postsurgical septic patient treated with 2 cycles of PMX-DHP using citrate anticoagulation. Monitoring of serum calcium, postcartridge calcium, and acid-base balance was performed. The treatments were accomplished without complications. To our knowledge, this is the first published report on the use of citrate anticoagulation during PMX-DHP. We conclude that citrate anticoagulation is feasible during hemoperfusion therapy in patients with increased hemorrhagic risk.

Use of a decision support system improves the management of hemodynamic and respiratory events in orthopedic patients under propofol sedation and spinal analgesia: a randomized trial.

Decision support systems (DSSs) have been successfully implemented into clinical practice offering clinical suggestions and treatment options with excellent results in various clinical settings. Although their results appeared promising, showing that DSSs can increase anesthesiologists' vigilance and patient safety during surgery, DSSs have never been used before to help anesthesiologists in identifying critical events in patients under spinal analgesia with sedation. We have developed and clinically evaluated a DSS for this specific task. The DSS was developed with the ability to indicate respiratory and hemodynamic critical events via audio-visual alarms and give decisional aid. Critical respiratory events were defined as SpO2 <92 % and/or respiratory rate <8/min. Critical hemodynamic events were defined as mean arterial pressure (MAP) <60 mmHg and/or heart rate <40 bpm. The objective of this trial was to determine the duration to detect and treat these critical events with the help of the DSS (DSS Group) compared with a standard Control Group where the system was not in place. One hundred and fifty orthopedic patients undergoing spinal analgesia with propofol sedation were enrolled in this randomized control trial, 75 each group. All respiratory and hemodynamic critical events were detected in the DSS Group, while in the Control Group 26 % of the events were not detected.The delay to detect and treat critical events was significantly shorter (P < 0.0001) in the DSS Group at 9.1 ± 3.6 s, whereas 27.5 ± 18.9 s were necessary to identify them in the Control Group. There were no significant differences in physiological parameters in the two groups during surgery. The number of critical events/h occurring and the duration of surgery were similar in both groups. The number of hypoxemia episodes was significantly less (P = 0.036) in the DSS group (0.7 ± 1.0 vs. 1.4 ± 2.2 for the Control Group). The DSS tested in this trial could help the clinician to detect and treat critical events more efficiently and in a shorter length of time.

A technical description of a novel pharmacological anesthesia robot.

To control the three components of general anesthesia (hypnosis, analgesia, and neuromuscular blockade), an automated closed-loop, anesthesia-drug delivery system (McSleepy) was developed. Bispectral index was used as the control variable for hypnosis, the analgoscore for analgesia, and phonomyography for neuromuscular blockade. McSleepy can be used to control the induction, maintenance and emergence from general anesthesia. To do so, a large touch screen is used to provide a user friendly interface, permitting bidirectional communication: the user giving information about the different stages of anesthesia, and the system prompting the anesthesiologist to perform certain actions such as mask ventilation, intubation or waking-up the patient using audio clips with voice commands. Several safety features were implemented to provide a secure and reliable anesthesia. Preliminary results of 15 patients are presented in this paper. Evaluation of McSleepy was done through an assessment of its clinical performance and using Varvel's performance indices. The system was found to be clinically useful by providing good precision in drug administration and reliable results for the duration of a general anesthesia.

Technical communication: First robotic ultrasound-guided nerve blocks in humans using the Magellan system.

BACKGROUND: Ultrasound-guided nerve blocks are becoming a standard of modern anesthesia. We developed a robotic system, Magellan, to perform nerve blocks using a remote control center. METHODS: Thirteen patients were enrolled in this pilot study. The Magellan system consists of 3 main components: a joystick, a robotic arm, and a software control system. The joystick allows simulation of wrist or arm movements of the proceduralist. After localization of the sciatic nerve, 35 mL of bupivacaine 0.25% was injected. The success rate of sciatic nerve blocks and block performance times (performance time=interval of time from the start of the ultrasound search for the nerve to the end of the injection of the drug; robotic time=interval of time from the identification of the nerve to the end of the injection of the drug) were determined. Data are presented as median (25th, 75th; minimal, maximal) and categorical data. RESULTS: Eight men and 5 women aged 34 years were included in this study. Nerve blocks were successful in all patients. A successful attempt was defined as the introduction of the needle into the nerve sheath; motor or sensory block was not used to determine the success rate. The nerve performance time was 189 seconds (150, 233; 90, 305), whereas the robotic time was 164 seconds (121, 210; 73, 271). CONCLUSIONS: We present the first human testing of a robotic ultrasound-guided nerve block system. The success rate was 100%. The total performance time was approximately 3 minutes to 4 minutes.

The Kepler intubation system.

Our goal in this study was to develop a robotic intubation system and to conduct a feasibility pilot study on the use of a robotic intubation system for endotracheal intubations. The Kepler Intubation System was developed, consisting of a remote control center (joystick and intubation cockpit) linked to a standard videolaryngoscope via a robotic arm. Ninety intubations were performed by the Kepler Intubation System on an airway trainer mannequin by a single operator. The first group of 30 intubations was performed with the operator in direct view of the mannequin (direct view group). The second group of 30 intubations was performed with the operator unable to see the mannequin (indirect view group). Thirty semiautomated intubations were also performed during which the robotic system replayed a trace of a previously recorded intubation maneuver (semiautomated group). First-attempt success rates and intubation times for each trial were recorded. Trends were analyzed using linear regression. Data are presented as mean (SD). All intubations were successful at first attempt. The mean intubation times were 46 (18) seconds, 51 (19) seconds, and 41 (1) seconds for the direct view, indirect view, and semiautomated group, respectively. Both the direct and indirect view groups had a negative slope, denoting that each successive trial required less time. The semiautomated group had a slope of 0 and a low SD of 1 second, illustrating the high reproducibility of automated intubations. We concluded that a robotic intubation system has been developed that can allow remote intubations within 40 to 60 seconds.

Robotic anesthesia - a vision for the future of anesthesia.

This narrative review describes a rationale for robotic anesthesia. It offers a first classification of robotic anesthesia by separating it into pharmacological robots and robots for aiding or replacing manual gestures. Developments in closed loop anesthesia are outlined. First attempts to perform manual tasks using robots are described. A critical analysis of the delayed development and introduction of robots in anesthesia is delivered.