In-bore MRI-compatible Transrectal Ultrasound and Photoacoustic Imaging.

Prostate cancer (PCa) is known as one of the most prevalent and fatal cancer types. This report describes an MRI-compatible photoacoustic/ultrasound (PA/US) imaging platform to improve the diagnosis of PCa. In the proposed solution, PA imaging, which offers real-time, non-ionizing imaging with high sensitivity and specificity, is combined with MRI, aiming to overcome PA's limited field of view (FOV) and make PA scalable for translation to clinical settings. Central to the design of the system is a reflector-based transrectal probing mechanism composed of MRI-compatible materials. The linear transducer with a center hole for optical fiber delivery can be mechanically actuated to form a multi-angled scan, allowing PA/US imaging from varied cross-sectional views. Performance assessment was carried out in phantom and ex-vivo settings. We confirmed the MRI compatibility of the system and demonstrated the feasibility of its tri-modal imaging capability by visualizing a tubing phantom containing contrast agents. The ex-vivo evaluation of targeted tumor imaging capability was performed with a mouse liver sample expressing PSMA-positive tumors, affirming the system's compatibility in spectroscopic PA (sPA) imaging with biological tissue. These results support the feasibility of the in-bore MRI-compatible transrectal PA and US and the potential clinical adaptability.

Opioids and immune checkpoint inhibitors differentially regulate a common immune network in triple-negative breast cancer.

Background: Opioids are the primary analgesics for cancer pain. Recent clinical evidence suggests opioids may counteract the effect of immune checkpoint inhibition (ICI) immunotherapy, but the mechanism for this interaction is unknown. The following experiments study how opioids and immunotherapy modulate a common RNA expression pathway in triple negative breast cancer (TNBC), a cancer subtype in which immunotherapy is increasingly used. This study identifies a mechanism by which opioids may decrease ICI efficacy, and compares ketamine, a non-opioid analgesic with emerging use in cancer pain, for potential ICI interaction. Methods: Tumor RNA expression and clinicopathologic data from a large cohort with TNBC (N=286) was used to identify RNA expression signatures of disease. Various drug-induced RNA expression profiles were extracted from multimodal RNA expression datasets and analyzed to estimate the RNA expression effects of ICI, opioids, and ketamine on TNBC. Results: We identified a RNA expression network in CD8+ T-cells that was relevant to TNBC pathogenesis and prognosis. Both opioids and anti-PD-L1 ICI regulated RNA expression in this network, suggesting a nexus for opioid-ICI interaction. Morphine and anti-PD-L1 therapy regulated RNA expression in opposing directions. By contrast, there was little overlap between the effect of ketamine and anti-PD-L1 therapy on RNA expression. Conclusions: Opioids and ICI may target a common immune network in TNBC and regulate gene expression in opposing fashion. No available evidence supports a similar interaction between ketamine and ICI.

Intraoperative laparoscopic photoacoustic image guidance system in the da Vinci surgical system.

This paper describes a framework allowing intraoperative photoacoustic (PA) imaging integrated into minimally invasive surgical systems. PA is an emerging imaging modality that combines the high penetration of ultrasound (US) imaging with high optical contrast. With PA imaging, a surgical robot can provide intraoperative neurovascular guidance to the operating physician, alerting them of the presence of vital substrate anatomy invisible to the naked eye, preventing complications such as hemorrhage and paralysis. Our proposed framework is designed to work with the da Vinci surgical system: real-time PA images produced by the framework are superimposed on the endoscopic video feed with an augmented reality overlay, thus enabling intuitive three-dimensional localization of critical anatomy. To evaluate the accuracy of the proposed framework, we first conducted experimental studies in a phantom with known geometry, which revealed a volumetric reconstruction error of 1.20 ± 0.71 mm. We also conducted an ex vivo study by embedding blood-filled tubes into chicken breast, demonstrating the successful real-time PA-augmented vessel visualization onto the endoscopic view. These results suggest that the proposed framework could provide anatomical and functional feedback to surgeons and it has the potential to be incorporated into robot-assisted minimally invasive surgical procedures.

Novel Cellular and Immunotherapy: Toxicities and Perioperative Implications.

Targeted cellular and immunotherapies have welcomed a new chapter in multi-modal cancer therapy. These agents harness our innate immune system and destroy malignant cells in a precise way as compared with "legacy" chemotherapeutic agents that largely rely on abolishing cell division. New therapies can augment the T-cell recognition of tumor antigens and effectively prevent tumor cells from their historically successful ability to evade immune recognition. These novel agents cause acute and chronic toxicities to a variety of organ systems (enteritis, pneumonitis, hypophysitis, and hepatitis), and this may masquerade as other chronic illnesses or paraneoplastic effects. As the perioperative footprint of cancer patients increases, it is essential that perioperative providers-anesthesiologists, surgeons, nurse anesthetists, and inpatient hospital medicine providers-be up to date on the physiologic mechanisms that underlie these new therapies as well as their acute and subacute toxicity profiles. Immunotherapy toxicity can significantly impact perioperative morbidity as well as influence perioperative management, such as prophylaxis for adrenal insufficiency, preoperative pulmonary assessment, and screening for thyroid dysfunction, among others.

Laparoscopic Photoacoustic Imaging System Based on Side-Illumination Diffusing Fibers.

OBJECTIVE: To develop a flexible miniaturized photoacoustic (PA) imaging probe for detecting anatomical structures during laparoscopic surgery. The proposed probe aimed to facilitate intraoperative detection of blood vessels and nerve bundles embedded in tissue not directly visible to the operating physician to preserve these delicate and vital structures. METHODS: We modified a commercially available ultrasound laparoscopic probe by incorporating custom-fabricated side-illumination diffusing fibers that illuminate the probe's field of view. The probe geometry, including the position and orientation of the fibers and the emission angle, was determined using computational models of light propagation in the simulation and subsequently validated through experimental studies. RESULTS: In wire phantom studies within an optical scattering medium, the probe achieved an imaging resolution of 0.43 ±0.09 mm and a signal-to-noise ratio of 31.2±1.84 dB. We also conducted an ex vivo study using a rat model, demonstrating the successful detection of blood vessels and nerves. CONCLUSION: Our results indicate the viability of a side-illumination diffusing fiber PA imaging system for guidance during laparoscopic surgery. SIGNIFICANCE: The potential clinical translation of this technology could enhance the preservation of critical vascular structures and nerves, thereby minimizing post-operative complications.

The use of transesophageal echocardiography to predict surgical complexity scoring system for degenerative mitral valve repair.

BACKGROUND: For severe mitral valve (MV) degenerative disease, repair is recommended. Prediction of repair complexity and referral to high volume centers can increase rates of successful repair. This study sought to demonstrate that TEE is a feasible imaging modality to predict the complexity of surgical MV repair. METHODS: Two hundred TEE examinations of patients who underwent MV repair (2009-2011) were retrospectively reviewed and scored by two cardiac anesthesiologists. TEE scores were compared to surgical complexity scores, which were previously assigned based on published methods. Kappa values were reported for the agreement of TEE and surgical scores. McNemar's tests were used to test the homogeneity of the marginal probabilities of different scoring categories. RESULTS: TEE scores were slightly lower (2[1,3]) than surgical scores (3[1,4]). The agreement was 66% between the scoring methods, with a moderate kappa (.46). Using surgical scores as the gold standard, 70%, 71%, and 46% of simple, intermediate and complex surgical scores, respectively, were correctly scored by TEE. P1, P2, P3, and A2 prolapse were easiest to identify with TEE and had the highest agreement with surgical scoring (P1 agreement 79% with kappa .55, P2 96% [kappa .8], P3 77% [kappa .51], A2 88% [kappa .6]). The lowest agreement between the two scores occurred with A1 prolapse (kappa .05) and posteromedial commissure prolapse (kappa .14). In the presence of significant disagreement, TEE scores were more likely to be of higher complexity than surgical. McNemar's test was significant for prolapse of P1 (p = .005), A1 (p = .025), A2 (p = .041), and the posteromedial commissure (p < .0001). CONCLUSION: TEE-based scoring is feasible for prediction of the complexity of MV surgical repair, thus allowing for preoperative stratification.

Individuals with moderate to severe hand impairments may struggle to use EMG control for assistive devices.

Neurological trauma, such as stroke, traumatic brain injury (TBI), spinal cord injury, and cerebral palsy can cause mild to severe upper limb impairments. Hand impairment makes it difficult for individuals to complete activities of daily living, especially bimanual tasks. A robotic hand orthosis or hand exoskeleton can be used to restore partial function of an intact but impaired hand. It is common for upper extremity prostheses and orthoses to use electromyography (EMG) sensing as a method for the user to control their device. However some individuals with an intact but impaired hand may struggle to use a myoelectrically controlled device due to potentially confounding muscle activity. This study was conducted to evaluate the application of conventional EMG control techniques as a robotic orthosis/exoskeleton user input method for individuals with mild to severe hand impairments. Nine impaired subjects and ten healthy subjects were asked to perform repeated contractions of muscles in their forearm and then onset analysis and feature classification were used to determine the accuracy of the employed EMG techniques. The average accuracy for contraction identification across employed EMG techniques was 95.4% ± 4.9 for the healthy subjects and 73.9% ± 13.1 for the impaired subjects with a range of 47.0% ± 19.1 - 91.6% ± 8.5. These preliminary results suggest that the conventional EMG control technologies employed in this paper may be difficult for some impaired individuals to use due to their unreliable muscle control.

What happens to brain outside the thermal ablation zones? An assessment of needle-based therapeutic ultrasound in survival swine.

BACKGROUND: In stereotactic radiosurgery, isodose lines must be considered to determine how surrounding tissue is affected. In thermal ablative therapy, such as laser interstitial thermal therapy (LITT), transcranial MR-guided focused ultrasound (tcMRgFUS), and needle-based therapeutic ultrasound (NBTU), how the surrounding area is affected has not been well studied. OBJECTIVE: We aimed to quantify the transition zone surrounding the ablation core created by magnetic resonance-guided robotically-assisted (MRgRA) delivery of NBTU using multi-slice volumetric 2-D magnetic resonance thermal imaging (MRTI) and subsequent characterization of the resultant tissue damage using histopathologic analysis. METHODS: Four swine underwent MRgRA NBTU using varying duration and wattage for treatment delivery. Serial MRI images were obtained, and the most representative were overlaid with isodose lines and compared to brain tissue acquired postmortem which underwent histopathologic analysis. These results were also compared to predicted volumes using a finite element analysis model. Contralateral brain tissue was used for control data. RESULTS: Intraoperative MRTI thermal isodose contours were characterized and comprehensively mapped to post-operative MRI images and qualitatively compared with histological tissue sections postmortem. NBTU 360° ablations induced smaller lesion volumes (33.19 mm3; 120 s, 3 W; 30.05 mm3, 180 s, 4 W) versus 180° ablations (77.20 mm3, 120 s, 3 W; 109.29 mm3; 180 s; 4 W). MRTI/MRI overlay demonstrated the lesion within the proximal isodose lines. The ablation-zone was characterized by dense macrophage infiltration and glial/neuronal loss as demonstrated by glial fibrillary acidic protein (GFAP) and neurofilament (NF) absence and avid CD163 staining. The transition-zone between lesion and normal brain demonstrated decreased macrophage infiltration and measured ∼345 microns (n - 3). We did not detect overt hemorrhages or signs of edema in the adjacent spared tissue. CONCLUSION: We successfully performed MRgRA NBTU ablation in swine and demonstrated minimal histologic changes extended past the ablation-zone. The lesion was characterized by macrophage infiltration and glial/neuronal loss which decreased through the transition-zone.

A sEMG Proportional Control for the Gripper of Patient Side Manipulator in da Vinci Surgical System.

There is a large community of people with hand disabilities, and these disabilities can be a barrier to those looking to retain or pursue surgical careers. With the development of surgical robotics technologies, it may be possible to develop user interfaces to accommodate these individuals. This paper proposes a hand-free control method for the gripper of a patient side manipulator (PSM) in the da Vinci surgical system. Using electromyography (EMG) signals, a proportional control method was tested on its ability to grasp a pressure sensor. These preliminary results demonstrate that the user can reliably control the grasping motion of the da Vinci PSM using this system. There is a strong correlation between grasping force and normalized EMG signal (r= 0.874). Moreover, the gripper can generate a step grasping force output when feeding in a generated step signal. The results in this paper demonstrate the system integration of a research EMG system with the da Vinci surgical system and are a step towards developing accessible teleoperation systems for surgeons with disabilities. Hand-free control for remaining degrees of freedom in the PSM is under development using additional input from the motion capture system.

Intraoperative opioids are associated with decreased recurrence rates in colon adenocarcinoma: a retrospective observational cohort study.

BACKGROUND: Opioid-induced immunomodulation may be important in colon adenocarcinoma, where tumour DNA mismatch repair (MMR) can determine the level of immune activation with consequences for therapeutic response and prognosis. We evaluated the relationship between intraoperative opioid exposure, MMR subtype, and oncological outcomes after surgery for colon adenocarcinoma. METHODS: Intraoperative opioid use (standardised by calculating morphine milligram equivalents) during stage I-III colon adenocarcinoma resection was reviewed retrospectively. Tumours were classified as DNA mismatch repair deficient (dMMR) or proficient (pMMR) by immunohistochemistry. The primary outcome was local tumour recurrence, distant tumour recurrence, or both (multivariable analysis). The exposures of interest were intraoperative analgesia and tumour subtype. Opioid-related gene expression was analysed using The Cancer Genome Atlas Colon Adenocarcinoma transcriptomic data. RESULTS: Clinical and pathological data were analysed from 1157 subjects (median age, 60 [51-70] yr; 49% female) who underwent curative resection for stage I-III colon adenocarcinoma. Higher intraoperative opioid doses were associated with reduced risk of tumour recurrence (hazard ratio=0.92 per 10 morphine milligram equivalents; 95% confidence interval [95% CI], 0.87-0.98; P=0.007), but not with overall survival. In tumours deficient in DNA MMR, tumour recurrence was less likely (HR=0.38; 95% CI, 0.21-0.68; P=0.001), with higher opioid dose associated with eightfold lower recurrence rates. Gene expression related to opioid signalling was different between dMMR and pMMR tumours. CONCLUSIONS: Higher intraoperative opioid dose was associated with a lower risk of tumour recurrence after surgery for stage I-III colon adenocarcinoma, but particularly so in tumours in which DNA MMR was deficient.

State of the Art and Future Opportunities in MRI-Guided Robot-Assisted Surgery and Interventions.

Magnetic resonance imaging (MRI) can provide high-quality 3-D visualization of target anatomy, surrounding tissue, and instrumentation, but there are significant challenges in harnessing it for effectively guiding interventional procedures. Challenges include the strong static magnetic field, rapidly switching magnetic field gradients, high-power radio frequency pulses, sensitivity to electrical noise, and constrained space to operate within the bore of the scanner. MRI has a number of advantages over other medical imaging modalities, including no ionizing radiation, excellent soft-tissue contrast that allows for visualization of tumors and other features that are not readily visible by other modalities, true 3-D imaging capabilities, including the ability to image arbitrary scan plane geometry or perform volumetric imaging, and capability for multimodality sensing, including diffusion, dynamic contrast, blood flow, blood oxygenation, temperature, and tracking of biomarkers. The use of robotic assistants within the MRI bore, alongside the patient during imaging, enables intraoperative MR imaging (iMRI) to guide a surgical intervention in a closed-loop fashion that can include tracking of tissue deformation and target motion, localization of instrumentation, and monitoring of therapy delivery. With the ever-expanding clinical use of MRI, MRI-compatible robotic systems have been heralded as a new approach to assist interventional procedures to allow physicians to treat patients more accurately and effectively. Deploying robotic systems inside the bore synergizes the visual capability of MRI and the manipulation capability of robotic assistance, resulting in a closed-loop surgery architecture. This article details the challenges and history of robotic systems intended to operate in an MRI environment and outlines promising clinical applications and associated state-of-the-art MRI-compatible robotic systems and technology for making this possible.

Amiodarone with or without N-Acetylcysteine for the Prevention of Atrial Fibrillation after Thoracic Surgery: A Double-blind, Randomized Trial.

BACKGROUND: Postoperative atrial fibrillation may identify patients at risk of subsequent atrial fibrillation, with its greater risk of stroke. This study hypothesized that N-acetylcysteine mitigates inflammation and oxidative stress to reduce the incidence of postoperative atrial fibrillation. METHODS: In this double-blind, placebo-controlled trial, patients at high risk of postoperative atrial fibrillation scheduled to undergo major thoracic surgery were randomized to N-acetylcysteine plus amiodarone or placebo plus amiodarone. On arrival to the postanesthesia care unit, N-acetylcysteine or placebo intravenous bolus (50 mg/kg) and then continuous infusion (100 mg/kg over the course of 48 h) was administered plus intravenous amiodarone (bolus of 150 mg and then continuous infusion of 2 g over the course of 48 h). The primary outcome was sustained atrial fibrillation longer than 30 s by telemetry (first 72 h) or symptoms requiring intervention and confirmed by electrocardiography within 7 days of surgery. Systemic markers of inflammation (interleukin-6, interleukin-8, tumor necrosis factor α, C-reactive protein) and oxidative stress (F2-isoprostane prostaglandin F2α; isofuran) were assessed immediately after surgery and on postoperative day 2. Patients were telephoned monthly to assess the occurrence of atrial fibrillation in the first year. RESULTS: Among 154 patients included, postoperative atrial fibrillation occurred in 15 of 78 who received N-acetylcysteine (19%) and 13 of 76 who received placebo (17%; odds ratio, 1.24; 95.1% CI, 0.53 to 2.88; P = 0.615). The trial was stopped at the interim analysis because of futility. Of the 28 patients with postoperative atrial fibrillation, 3 (11%) were discharged in atrial fibrillation. Regardless of treatment at 1 yr, 7 of 28 patients with postoperative atrial fibrillation (25%) had recurrent episodes of atrial fibrillation. Inflammatory and oxidative stress markers were similar between groups. CONCLUSIONS: Dual therapy comprising N-acetylcysteine plus amiodarone did not reduce the incidence of postoperative atrial fibrillation or markers of inflammation and oxidative stress early after major thoracic surgery, compared with amiodarone alone. Recurrent atrial fibrillation episodes are common among patients with postoperative atrial fibrillation within 1 yr of major thoracic surgery.

The Influence of Life History on the Response to Parasitism: Differential Response to Non-Lethal Sea Lamprey Parasitism by Two Lake Charr Ecomorphs.

The energetic demands of stressors like parasitism require hosts to reallocate energy away from normal physiological processes to survive. Life history theory provides predictions about how hosts will reallocate energy following parasitism, but few studies provide empirical evidence to test these predictions. We examined the sub-lethal effects of sea lamprey parasitism on lean and siscowet lake charr, two ecomorphs with different life history strategies. Leans are shorter lived, faster growing, and reach reproductive maturity earlier than siscowets. Following a parasitism event of 4 days, we assessed changes to energy allocation by monitoring endpoints related to reproduction, energy storage, and growth. Results indicate that lean and siscowet lake charr differ considerably in their response to parasitism. Severely parasitized leans slightly increased their reproductive effort and maintained growth and energy storage, consistent with expectations based on life history that leans are less likely to survive parasitism and have shorter lifespans than siscowets making investing in immediate reproduction more adaptive. Siscowets nearly ceased reproduction following severe parasitism and showed evidence of altered energy storage, consistent with a strategy that favors maximizing long-term reproductive success. These findings suggest that life history can be used to generalize stressor response between populations and can aid management efforts.

The association between modifiable perioperative parameters and renal function after nephrectomy.

OBJECTIVE: To evaluate the association between intraoperative anaesthetic parameters, primarily intraoperative hypotension, and postoperative renal function in patients undergoing nephrectomy. PATIENTS AND METHODS: We reviewed data from 3240 consecutive patients who underwent nephrectomy between 2010 and 2018. Anaesthetic parameters evaluated included duration of hypotension, tachycardia, hypothermia, volatile anaesthetic use and mean arterial pressure in the post-anaesthesia care unit. Outcomes included acute kidney injury (AKI) and estimated glomerular filtration rate (eGFR) within the first year after nephrectomy. Associations between anaesthetic parameters and outcomes were evaluated with multivariable logistic regression and generalised estimating equation, respectively, adjusted for predictors of renal function after nephrectomy. RESULTS: Before nephrectomy, 677 (21%) patients had moderate-severe chronic kidney disease. A quarter of patients (n = 809) had postoperative AKI and 35% (n = 746) had Stage ≥3 chronic kidney disease 12-months after surgery. Only 12% of patients (n = 386) had >5 min of intraoperative hypotension. While not statistically significant, longer duration of intraoperative hypotension was associated with slightly higher rates of AKI (odds ratio [OR] per 10-min 1.14, 95% confidence interval [CI] 0.98, 1.32). Prolonged hypothermia was associated with increased rate of AKI (OR per 10-min 1.02, 95% CI 1.00, 1.04), and decreased eGFR (change in eGFR per 10-min -0.19, 95% CI -0.27, -0.12); however, these results have limited clinical significance. CONCLUSIONS: Under current practice, intraoperative anaesthetic parameters are tightly maintained, restricting the significance of their effect on postoperative renal function. Future studies should evaluate whether haemodynamic parameters during the early postoperative period, when they are monitored less frequently, are associated with renal functional outcome.

Intraoperative haemodynamics and postoperative intensive care unit admission in older patients with cancer.

PURPOSE: Research on the impact of various intraoperative haemodynamic variables on the incidence of postoperative ICU admission among older patients with cancer is limited. In this study, the relationship between intraoperative haemodynamic status and postoperative intensive care unit admission among older patients with cancer is explored. METHODS: Patients aged ≥75 who underwent elective oncologic surgery lasting ≥120min were analysed. Chi-squared and t-tests were used to assess the associations between intraoperative variables with postoperative intensive care unit admission. Multivariable regressions were used to analyse potential predict risk factors for postoperative intensive care unit admission. RESULTS: Out of 994 patients, 48 (4.8%) were admitted to the intensive care unit within 30 days following surgery. Intensive care unit admission was associated with the presence of ≥4 comorbid conditions, intraoperative blood loss ≥100mL, and intraoperative tachycardia and hypertensive urgency. On multivariable analysis, operation time ≥240min (Odds Ratio [OR] = 2.29, p = 0.01), and each minute spent with intraoperative hypertensive urgency (OR = 1.06, p = 0.01) or tachycardia (OR = 1.01, p = 0.002) were associated with postoperative intensive care unit admission. CONCLUSION: Intraoperative hypertensive urgency and tachycardia were associated with postoperative intensive care unit admission in older patients undergoing cancer surgery.

Control of a lower limb exoskeleton using Learning from Demonstration and an iterative Linear Quadratic Regulator Controller: A simulation study.

Lower limb exoskeletons have complex dynamics that mimic human motion. They need to be able to replicate lower limb motion such as walking. The trajectory of the exoskeleton joints and the control signal generated are essential to the system's operation. Current learning from demonstration methods has only been combined with linear quadratic regulators; this limits the applicability of processes since most robotic systems have non-linear dynamics. The Asynchronous Multi-Body Framework simulates the dynamics and allows for real-time control. Eleven gait cycle demonstrations were recorded from volunteers using motion capture and encoded using Task Parameterized Gaussian mixture models. An iterative linear quadratic regulator is used to find an optimal control signal to drive the exoskeleton joints through the desired trajectories. A PD controller is added as a feed-forward control component for unmodeled dynamics and optimized using the Bayesian Information Criterion. We show how the trajectory is learned, and the control signal is optimized by reducing the required bins for learning. The framework presented produces optimal control signals to allow the exoskeleton's legs to follow human motion demonstrations.

Open source Vicon Toolkit for motion capture and Gait Analysis.

BACKGROUND AND OBJECTIVE: The Vicon motion capture system is a popular tool for biomechanics, gait analysis, and robotics. The ASCII files produced are large and complex, making them difficult to read and analyze. METHODS: This paper presents two packages, the Vicon Toolkit Package and the Gait Analysis Toolkit Package. They use an open-source framework for ingesting, parsing, and analyzing Vicon mocap data and performing gait analysis. The package that handles the Vicon analysis is separated from the Gait Analysis package to allow for abstraction and expansion, and is not specific only to the Vicon system. RESULTS: Our Vicon Toolkit provides tools to work directly with the marker data and other Vicon Nexus system outputs. The Gait Toolkit provides tools for performing gait analysis, EMG filtering, and learning trajectories. The packages are built upon a core library, GaitCore, that provides unified objects to perform operations and store data. CONCLUSION: This paper will show how to use the packages' tools and the expected outputs. All the tools are open-source and written in Python3.x for ease of use and access to other powerful libraries.

ROUTINE USE OF SUGAMMADEX DOES NOT SHORTEN PACU LENGTH OF STAY: A PROSPECTIVE DOUBLE-BLINDED RANDOMIZED CONTROLLED TRIAL.

BACKGROUND: The reversal agent sugammadex has been shown to be more efficacious at reversal from neuromuscular blockade (NMB) induced by the aminosteroid class of non-depolarizing muscle relaxants than the traditionally used medication neostigmine. However, whether these differences lead to significantly faster PACU discharge readiness remains unknown. Given the increased acquisition cost of sugammadex as compared to neostigmine we compared these two reversal agents in our surgical population to determine if its pharmacokinetic superiority warranted a change in current practice. METHODS: We conducted a single-center randomized patient and assessor blinded clinical trial. A total of 201 patients presenting for surgery requiring NMB with an estimated duration of ≤ 6 hours were included in the intention-to-treat (ITT) analysis. The primary outcome was time from reversal agent administration to PACU discharge readiness, measured by either the institutional discharge scoring tool or bedside clinical assessment by a PACU physician or advanced practice provider. Secondary outcomes included subjective assessment of recovery by the patient (pain, visual changes, speaking difficulty, swallowing difficulty, PONV, anxiety) and a simple strength assessment. RESULTS: Median time from reversal administration to PACU discharge readiness was 3.59 hours (IQR 2.49-5.09) in the neostigmine group and 3.62 hours (IQR 2.70-5.87) in the sugammadex group. Patients who received sugammadex had 8% longer reversal to PACU discharge times (exp(estimate) 1.08, 95% CI [0.87-1.34], p=0.499). Patients age 70 or older had 28% longer reversal to PACU discharge times (exp(estimate) of 1.28, 95% CI [0.91-1.80], P=0.158). In the a modified ITT analysis, sugammadex patients were estimated to be in PACU 13% longer than neostigmine arm patients (exp(estimate) 1.13, 95% CI [0.91-1.40], p=0.265) and patients older than or equal to 70 years 31% longer than patients less than 70 years old (exp(estimate) 1.31, 95% CI [0.93-1.84], p=0.121). Treatment arm was not associated with any of the secondary outcomes. CONCLUSION: There was no significant difference in time to readiness to discharge from PACU, and there were no subjective or objective clinically relevant differences in recovery from neuromuscular blockade between the groups. Findings of this study support continued use of either agent at the anesthesiologist's discretion.

Intraoperative opioid exposure, tumour genomic alterations, and survival differences in people with lung adenocarcinoma.

BACKGROUND: Opioids have been linked to worse oncologic outcomes in surgical patients. Studies in certain cancer types have identified associations between survival and intra-tumoural opioid receptor gene alterations, but no study has investigated whether the tumour genome interacts with opioid exposure to affect survival. We sought to determine whether intraoperative opioid exposure is associated with recurrence-specific survival and overall survival in early-stage lung adenocarcinoma, and whether selected tumour genomics are associated with this relationship. Associations between ketamine and dexmedetomidine and outcomes were also studied. METHODS: Surgical patients (N=740) with pathological stage I-III lung adenocarcinoma and next-generation sequencing data were retrospectively reviewed from a prospectively maintained database. RESULTS: On multivariable analysis, ketamine administration was protective for recurrence-specific survival (hazard ratio = 0.44, 95% confidence interval 0.24-0.80; P=0.007), compared with no adjunct. Higher intraoperative oral morphine milligram equivalents were significantly associated with worse overall survival (hazard ratio=1.09/10 morphine milligram equivalents, 95% confidence interval 1.02-1.17; P=0.010). Significant interaction effects were found between morphine milligram equivalents and fraction genome altered and morphine milligram equivalents and CDKN2A, such that higher fraction genome altered or CDKN2A alterations were associated with worse overall survival at higher morphine milligram equivalents (P=0.044 and P=0.052, respectively). In contrast, alterations in the Wnt (P=0.029) and Hippo (P=0.040) oncogenic pathways were associated with improved recurrence-specific survival at higher morphine milligram equivalents, compared with unaltered pathways. CONCLUSIONS: Intraoperative opioid exposure is associated with worse overall survival, whereas ketamine exposure is associated with improved recurrence-specific survival in patients with early-stage lung adenocarcinoma. This is the first study to investigate tumour-specific genomic interactions with intraoperative opioid administration to modify survival associations.