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.

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 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.

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.

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.

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.

Outcomes After Multidisciplinary Management of Primary Mediastinal Germ Cell Tumors.

OBJECTIVE: We examined management strategies, overall survival (OS), and progression-free survival (PFS) among patients with PMNSGCTs undergoing resection and multidisciplinary management at a high-volume institution. SUMMARY OF BACKGROUND DATA: Outcomes after resection of PMNSGCTs are not well-characterized, with limited data on factors associated with survival. METHODS: We reviewed patients with PMNSGCT who underwent resection between 1980 and 2019. Median follow-up was 3.4 years. Preoperative therapy (including use of bleomycin), surgical management, recurrence, and survival were examined. Factors associated with survival were analyzed using Cox regression. RESULTS: In total, 113 patients were included [median age, 28 years (range, 16-65)]. Preoperative serum tumor markers (STMs) normalized/decreased in 74% of patients. Pathology included necrosis only (25%), teratoma +/- necrosis (20%), viable nonteratomatous germ cell tumor +/- teratoma (41%), and secondary somatic-type malignancy +/- teratoma (20%). Bleomycin chemotherapy was not associated with pulmonary complications or 90-day mortality. Patients receiving second-line chemotherapy followed by resection had significantly worse OS and PFS than patients receiving first-line chemotherapy followed by resection. On multivariable analysis, R1/R2 resection (HR, 3.92; P < 0.001) and increasing postoperative STMs (HR, 4.98; P < 0.001) were associated with shorter PFS; necrosis on pathology (HR, 0.42, P = 0.043) was associated with longer PFS. CONCLUSIONS: In patients with PMNSGCT undergoing resection, completeness of resection, postoperative pathology, and postoperative STMs were associated with PFS. Induction bleomycin was not associated with pulmonary complications or mortality in patients undergoing resection. Patients undergoing second-line chemotherapy followed by resection have a poor prognosis, with long-term survival of 22%.

Intraoperative opioids are associated with improved recurrence-free survival in triple-negative breast cancer.

BACKGROUND: Opioid-induced immunomodulation may be of particular importance in triple-negative breast cancer (TNBC) where an immune response is associated with improved outcome and response to immunotherapy. We evaluated the association between intraoperative opioids and oncological outcomes and explored patterns of opioid receptor expression in TNBC. METHODS: Consecutive patients with stage I-III primary TNBC were identified from a prospectively maintained database. Opioid receptor expression patterns in the tumour microenvironment were analysed using publicly available bulk and single-cell RNA-seq data. RESULTS: A total of 1143 TNBC cases were retrospectively analysed. In multivariable analysis, higher intraoperative opioid dose was associated with favourable recurrence-free survival, hazard ratio 0.93 (95% confidence interval 0.88-0.99) per 10 oral morphine milligram equivalents increase (P=0.028), but was not significantly associated with overall survival, hazard ratio 0.96 (95% confidence interval 0.89-1.02) per 10 morphine milligram equivalents increase (P=0.2). Bulk RNA-seq analysis of opioid receptors showed that OPRM1 was nearly non-expressed. Compared with normal breast tissue OGFR, OPRK1, and OPRD1 were upregulated, while TLR4 was downregulated. At a single-cell level, OPRM1 and OPRD1 were not detectable; OPRK1 was expressed mainly on tumour cells, whereas OGFR and TLR4 were more highly expressed on immune cells. CONCLUSIONS: We found a protective effect of intraoperative opioids on recurrence-free survival in TNBC. Opioid receptor expression was consistent with a net protective effect of opioid agonism, with protumour receptors either not expressed or downregulated, and antitumour receptors upregulated. In this era of personalised medicine, efforts to differentiate the effects of opioids across breast cancer subtypes (and ultimately individual patients) should continue.

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.

Predicting ablation zones with multislice volumetric 2-D magnetic resonance thermal imaging.

BACKGROUND: High-intensity focused ultrasound (HIFU) serves as a noninvasive stereotactic system for the ablation of brain metastases; however, treatments are limited to simple geometries and energy delivery is limited by the high acoustic attenuation of the calvarium. Minimally-invasive magnetic resonance-guided robotically-assisted (MRgRA) needle-based therapeutic ultrasound (NBTU) using multislice volumetric 2-D magnetic resonance thermal imaging (MRTI) overcomes these limitations and has potential to produce less collateral tissue damage than current methods. OBJECTIVE: To correlate multislice volumetric 2-D MRTI volumes with histologically confirmed regions of tissue damage in MRgRA NBTU. METHODS: Seven swine underwent a total of 8 frontal MRgRA NBTU lesions. MRTI ablation volumes were compared to histologic tissue damage on brain sections stained with 2,3,5-triphenyltetrazolium chloride (TTC). Bland-Altman analyses and correlation trends were used to compare MRTI and TTC ablation volumes. RESULTS: Data from the initial and third swine's ablations were excluded due to sub-optimal tissue staining. For the remaining ablations (n = 6), the limits of agreement between the MRTI and histologic volumes ranged from -0.149 cm3 to 0.252 cm3 with a mean difference of 0.052 ± 0.042 cm3 (11.1%). There was a high correlation between the MRTI and histology volumes (r2 = 0.831) with a strong linear relationship (r = 0.868). CONCLUSION: We used a volumetric MRTI technique to accurately track thermal changes during MRgRA NBTU in preparation for human trials. Improved volumetric coverage with MRTI enhanced our delivery of therapy and has far-reaching implications for focused ultrasound in the broader clinical setting.

The Association of Cerebral Desaturation During One-Lung Ventilation and Postoperative Recovery: A Prospective Observational Cohort Study.

OBJECTIVES: This study was designed to investigate whether cerebral oxygen desaturations during thoracic surgery are predictive of patients' quality of recovery. As a secondary aim, the authors investigated the relationship among cerebral desaturations and postoperative delirium and hospital length of stay. DESIGN: This study was a prospective observational cohort study. SETTING: A single tertiary-care medical center from September 2012 through March 2014. PATIENTS: Adult patients scheduled for elective pulmonary surgery requiring one-lung ventilation. INTERVENTIONS: All patients were monitored with the ForeSight cerebral oximeter. MEASUREMENTS AND MAIN RESULTS: The primary assessment tool was the Postoperative Quality of Recovery Scale. Delirium was assessed using the Confusion Assessment Method. Of the 117 patients analyzed in the study, 60 of the patients desaturated below a cerebral oximetry level of 65% for a minimum of 3 minutes (51.3%). Patients who desaturated were significantly less likely to have cognitive recovery in the immediate postoperative period (p = 0.012), which did not persist in the postoperative period beyond day 0. Patients who desaturated also were more likely to have delirium (p = 0.048, odds ratio 2.81 [95% CI 1.01-7.79]) and longer length of stay (relative duration 1.35, 95% CI 1.05-1.73; p = 0.020). CONCLUSIONS: Intraoperative cerebral oxygen desaturations, frequent during one-lung ventilation, are associated significantly with worse early cognitive recovery, high risk of postoperative delirium, and prolonged length of stay. Large interventional studies on cerebral oximetry in the thoracic operating room are warranted.

Pericardial Effusions in Patients With Cancer: Anesthetic Management and Survival Outcomes.

OBJECTIVES: The objective of this study was to describe practice patterns of anesthetic management during pericardial window creation. DESIGN: Retrospective observational cohort study. SETTING: Single tertiary cancer center. PARTICIPANTS: A total of 150 patients treated for cancer between 2011 and 2015 were included in the study. MEASUREMENTS AND MAIN RESULTS: The primary objective was to evaluate anesthetic management in pericardial window creation. Secondary outcomes were 30-day mortality and overall survival after pericardial window creation. Thirty-day mortality was 19.3%, and median survival was 5.84 months. Higher American Society of Anesthesiologists (ASA) physical status of patients was associated with preinduction arterial line placement (51% ASA 3 v 79% ASA 4; p = 0.002) and use of etomidate for anesthetic induction (34% ASA 3 v 60% ASA 4; p = 0.003). However, there was no association between anesthetic management and presence of tamponade in these patients. Cardiac aspirate volume (per 10 mL: odds ratio [OR], 1.02 [95% CI, 1.0-1.04]; p = 0.026) and intraoperative arrhythmia (atrial fibrillation: OR, 6.76 [95% CI, 1.2-37.49]; p = 0.029; sinus tachycardia: OR, 4.59 [95% CI, 1.25-16.90]; p = 0.022) were associated independently with increased 30-day mortality. High initial heart rate (per 10 beats per minute: hazard ratio [HR], 1.18 [95% CI, 1.05-1.33]; p = 0.005) in the operating room and intraoperative sinus tachycardia (HR, 1.86 [95% CI, 1.15-3.03]; p = 0.012) were associated independently with worse overall survival. CONCLUSION: Risk of death after pericardial window creation remains high in patients with cancer. Variations in anesthetic management did not affect survival in oncologic patients with pericardial effusions.

Use of vasopressors during esophagectomy is not associated with increased risk of anastomotic leak.

Vasopressor use during esophagectomy has been reported to increase the risk of postoperative anastomotic leak and associated morbidity. We sought to assess the association between vasopressor use and fluid (crystalloid and colloid) administration and anastomotic leak following open esophagectomy. Patients who underwent open Ivor Lewis esophagectomy were identified from a prospective institutional database. The primary outcome was postoperative anastomotic leak (any grade) and analyzed using logistic regression models. Postoperative anastomotic leak developed in 52 of 327 consecutive patients (16%) and was not significantly associated with vasopressor use or fluid administered in either univariable or multivariable analyses. Increasing body mass index was the only significant characteristic of both univariable (P = 0.004) and multivariable analyses associated with anastomotic leak (odds ratio, 1.05; 95% confidence interval, 1.01-1.09; P = 0.007). Of the 52 patients that developed an anastomotic leak, 12 (23%) were grade 1, 21 (40%) were grade 2 and 19 (37%) were grade 3. In our cohort, only body mass index, and not intraoperative vasopressor use and fluid administration, was significantly associated with increased odds of postoperative anastomotic leak following open Ivor Lewis esophagectomy.

Using near-infrared spectroscopy myocardial oximetry to monitor myocardial oxygen balance in a swine model of cardiac surgery: a descriptive study.

Monitoring of the adequacy of myocardial protection with cardioplegia is nearly non-existent in clinical cardiac surgical practice and instead relies on well-defined protocols for delivery of cardioplegia often resulting in inadequate protection. We hypothesized that Near Infrared Spectroscopy technology could be useful in the monitoring of the myocardial oxygen state by attaching the monitors to the epicardium in a porcine model of cardiac surgery. The experiments were conducted with 3 different protocols of 2 pigs each for a total of 6 pigs. The objective was to induce episodic, oxygen supply-demand mismatch. Methods for decreased supply included decreasing coronary blood flow, coronary blood hypoxemia, coronary occlusion, hypovolemia, and hypotension. Methods for increase demand included rapid ventricular pacing and the administration of isoproterenol. Changes in myocardial tissue oximetry were measured and this measurement was then correlated with blood hemoglobin saturations of oxygen from coronary sinus blood samples. We found that decreases in myocardial oxygen supply or increases in demand due to any of the various experimental conditions led to decreases in both myocardial tissue oximetry and hemoglobin oxygen saturation of coronary sinus blood with recovery when the conditions were returned to baseline. Correlation between myocardial tissue oximetry and hemoglobin oxygen saturation of coronary sinus blood was moderate to strong under all tested conditions. This may have translational applications as a monitor of adequacy of myocardial protection and the detection of coronary occlusion.

A Fully Actuated Robotic Assistant for MRI-Guided Precision Conformal Ablation of Brain Tumors.

This paper reports the development of a fully actuated robotic assistant for magnetic resonance imaging (MRI)-guided precision conformal ablation of brain tumors using an interstitial high intensity needle-based therapeutic ultrasound (NBTU) ablator probe. The robot is designed with an eight degree-of-freedom (DOF) remote center of motion (RCM) manipulator driven by piezoelectric actuators, five for aligning the ultrasound thermal ablator to the target lesions and three for inserting and orienting the ablator and its cannula to generate a desired ablation profile. The 8-DOF fully actuated robot can be operated in the scanner bore during imaging; thus, alleviating the need of moving the patient in or out of the scanner during the procedure, and therefore potentially reducing the procedure time and streamlining the workflow. The free space positioning accuracy of the system is evaluated with the OptiTrack motion capture system, demonstrating the root mean square (RMS) error of the tip position to be 1.11±0.43mm. The system targeting accuracy in MRI is assessed with phantom studies, indicating the RMS errors of the tip position to be 1.45±0.66mm and orientation to be 1.53±0.69°. The feasibility of the system to perform thermal ablation is validated through a preliminary ex-vivo tissue study with position error less than 4.3mm and orientation error less than 4.3°.

Immune checkpoint inhibitors: a narrative review of considerations for the anaesthesiologist.

Immunotherapy has revolutionised the treatment of oncologic malignancies. Immune checkpoint inhibitors represent a new class of immunotherapy drugs. Although these drugs show promise, they are associated with immune-related adverse reactions. An increasing number of patients who undergo surgery will have had treatment with immune checkpoint inhibitors. In this narrative review article, we discuss their mechanism of action, therapeutic effects, pertinent toxicities, and address specific perioperative considerations for patients treated with immune checkpoint inhibitors.

COVID-19 in the Cancer Patient.

The novel coronavirus disease 2019 (COVID-19) was first reported in China in December 2019. Since then, it has spread across the world to become one of the most serious life-threatening pandemics since the influenza pandemic of 1918. This review article will focus on the specific risks and nuanced considerations of COVID-19 in the cancer patient. Important perioperative management recommendations during this outbreak are emphasized, in addition to discussion of current treatment techniques and strategies available in the battle against COVID-19.

Institution of Monthly Anesthesia Quality Reports Does Not Reduce Postoperative Complications despite Improved Metric Compliance.

While quality programs have been shown to improve provider compliance, few have demonstrated conclusive improvements in patient outcomes. We hypothesized that there would be increased metric compliance and decreased postoperative complications after initiation of an anesthesiology quality improvement program at our institution. We performed a retrospective study of all adult inpatients having anesthesia for a twelve-month period that spanned six months before and after program implementation. The primary outcome was the rate of complications in the post-implementation period. Secondary outcomes included the change in proportion of complications and compliance with quality metrics. We studied a total of 9620 adult inpatient cases, subdivided into pre- and post-implementation groups (4832 vs 4788.) After multivariate model adjustment, the rate of any complication (our primary outcome) was not significantly changed (32% to 31%; adjusted P = 0.410.) Of the individual complications, only wound infection (2.0% to 1.5%; adjusted P = 0.020) showed a statistically significant decrease. Statistically and clinically significant increases in compliance were seen for the BP-02 Avoiding Monitoring Gaps metric (81% to 93%, P < 0.001), both neuromuscular blockade metrics (NMB-01 76% to 91%, P < 0.001; NMB-02 95% to 97%, P = 0.006), both tidal volume metrics (PUL-01 84% to 93%, P < 0.001; PUL-02 30% to 45%, P < 0.001), and the TEMP-02 Core Temperature Measurement metric (88% to 94%, P < 0.001). Implementation of a comprehensive quality feedback program improved metric compliance but was not associated with a change in postoperative complications.

Identification of Abundant and Evolutionarily Conserved Opioid Receptor Circular RNAs in the Nervous System Modulated by Morphine.

Circular RNAs (circRNAs) are a distinct category of single-stranded, covalently closed RNAs formed by backsplicing. The functions of circRNAs are incompletely known and are under active investigation. Here, we report that in addition to traditional linear mRNAs (linRNA), mouse, rat, and human opioid receptor genes generate exonic circRNA isoforms. Using standard molecular biologic methods, Oprm1 circRNAs (circOprm1) were detected in RNAs of rodent and human brains and spinal cords, as well as human neuroblastoma cells, suggesting evolutionary conservation. Sequencing confirmed backsplicing using canonical splice sites. Oprm1 circRNAs were sense-stranded circRNAs resistant to RNase R digestion. The relative abundance of Oprm1 circRNA to linRNA determined by quantitative reverse transcription polymerase chain reaction varied among mouse brain regions, with circRNA isoforms predominating in rostral structures and less abundant in brain stem. Chronic morphine exposure in mice increased brain circOprm1e2.3 and circOprm1.e2.e3.e4(302) levels by 1.5- to 1.6-fold relative to linRNA. Sequence analysis predicted numerous microRNA binding sites within Oprm1 circRNA sequences, suggesting a potential role in microRNA sequestration through sponging. In addition, we observed that other opioid receptor genes including δ, κ, and nociceptin receptor genes produced similar circRNAs. In conclusion, all members of the opioid receptor gene family express circRNAs, with Oprm1 circRNA levels exceeding those of linear forms in some regions. SIGNIFICANCE STATEMENT: The modulation of Oprm1 circular RNA (circRNA) expression by morphine, coupled with the high abundance and existence of potential miRNA binding sites with circRNA sequences suggests the potential role of Oprm1 circRNAs in chronic opioid effects such as tolerance.

Next Generation of Cancer Treatments: Chimeric Antigen Receptor T-Cell Therapy and Its Related Toxicities: A Review for Perioperative Physicians.

Cancer immunotherapy has entered a new era with the recent introduction of genetically engineered T-cells that express chimeric antigen receptors (CARs) capable of recognizing and destroying tumor cells. Several clinical trials in patients with relapsed or refractory B-cell malignancies have demonstrated complete remission rates ranging from 50% to 90%, with long-term data suggestive of a possible curative response. CAR T-cell therapy is currently under investigation for earlier use in these disease processes and in various other solid and liquid tumors. CAR T-cell therapy is associated with a unique postinfusion toxicity profile including cytokine-release syndrome and neurotoxicity. These toxicities are usually reversible but can be fatal, requiring close vigilance and prompt treatment often in an intensive care unit (ICU) setting. CAR T-cell therapy is currently restricted to designated centers possessing expertise in acute toxicity management, but wider use is likely if early therapeutic successes are replicated. As perioperative and critical care physicians, anesthesiologists may encounter such patients in the perioperative or ICU setting and should become familiar with this unique and novel therapeutic modality capable of causing extreme cardiovascular and respiratory compromise. This review will describe the immunobiology of CAR T-cells, their relevance to cancer treatment, clinical aspects of their therapeutic use in cancer chemotherapy, toxicities related to CAR T-cell use, and their therapeutic management.