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1.
Front Oncol ; 13: 1267532, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37781176

RESUMEN

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.

2.
Echocardiography ; 40(6): 562-567, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37212377

RESUMEN

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.


Asunto(s)
Ecocardiografía Tridimensional , Enfermedades de las Válvulas Cardíacas , Insuficiencia de la Válvula Mitral , Prolapso de la Válvula Mitral , Humanos , Ecocardiografía Transesofágica/métodos , Válvula Mitral/diagnóstico por imagen , Prolapso de la Válvula Mitral/cirugía , Estudios Retrospectivos , Ecocardiografía Tridimensional/métodos , Insuficiencia de la Válvula Mitral/cirugía , Prolapso
3.
Br J Anaesth ; 129(2): 172-181, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35718564

RESUMEN

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.


Asunto(s)
Adenocarcinoma , Neoplasias del Colon , Adenocarcinoma/genética , Adenocarcinoma/cirugía , Analgésicos Opioides/uso terapéutico , Neoplasias del Colon/genética , Neoplasias del Colon/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Derivados de la Morfina/uso terapéutico , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos
4.
Anesthesiology ; 136(6): 916-926, 2022 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-35263434

RESUMEN

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.


Asunto(s)
Amiodarona , Fibrilación Atrial , Cirugía Torácica , Acetilcisteína/uso terapéutico , Amiodarona/uso terapéutico , Antiarrítmicos/uso terapéutico , Fibrilación Atrial/epidemiología , Fibrilación Atrial/etiología , Fibrilación Atrial/prevención & control , Puente de Arteria Coronaria/efectos adversos , Método Doble Ciego , Humanos , Inflamación/complicaciones , Complicaciones Posoperatorias/tratamiento farmacológico , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & control
5.
J Perioper Pract ; 32(11): 301-309, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-34134558

RESUMEN

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.


Asunto(s)
Neoplasias , Admisión del Paciente , Humanos , Anciano , Unidades de Cuidados Intensivos , Procedimientos Quirúrgicos Electivos , Factores de Riesgo , Neoplasias/cirugía , Hemodinámica , Estudios Retrospectivos , Complicaciones Posoperatorias/epidemiología
6.
BJU Int ; 129(3): 380-386, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34196093

RESUMEN

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.


Asunto(s)
Lesión Renal Aguda , Carcinoma de Células Renales , Hipotensión , Hipotermia , Neoplasias Renales , Insuficiencia Renal Crónica , Lesión Renal Aguda/etiología , Carcinoma de Células Renales/cirugía , Femenino , Tasa de Filtración Glomerular , Humanos , Hipotensión/etiología , Hipotensión/cirugía , Hipotermia/cirugía , Riñón/cirugía , Neoplasias Renales/cirugía , Masculino , Nefrectomía/efectos adversos , Nefrectomía/métodos , Complicaciones Posoperatorias , Estudios Retrospectivos
7.
Artículo en Inglés | MEDLINE | ID: mdl-34504958

RESUMEN

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.

9.
Br J Anaesth ; 127(1): 75-84, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34147159

RESUMEN

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.


Asunto(s)
Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/cirugía , Analgésicos Opioides/efectos adversos , Genómica/tendencias , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirugía , Recurrencia Local de Neoplasia/genética , Adenocarcinoma del Pulmón/mortalidad , Anciano , Analgésicos Opioides/administración & dosificación , Femenino , Humanos , Cuidados Intraoperatorios/efectos adversos , Cuidados Intraoperatorios/tendencias , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/diagnóstico , Recurrencia Local de Neoplasia/epidemiología , Dolor Postoperatorio/prevención & control , Estudios Prospectivos , Estudios Retrospectivos , Tasa de Supervivencia/tendencias
10.
J Cardiothorac Vasc Anesth ; 35(2): 542-550, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32861541

RESUMEN

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.


Asunto(s)
Circulación Cerebrovascular , Ventilación Unipulmonar , Adulto , Humanos , Ventilación Unipulmonar/efectos adversos , Oximetría , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Periodo Posoperatorio , Estudios Prospectivos
11.
Dis Esophagus ; 34(4)2021 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-32944749

RESUMEN

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.


Asunto(s)
Neoplasias Esofágicas , Esofagectomía , Anastomosis Quirúrgica/efectos adversos , Fuga Anastomótica/etiología , Neoplasias Esofágicas/cirugía , Esofagectomía/efectos adversos , Humanos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Estudios Prospectivos , Estudios Retrospectivos
12.
J Clin Monit Comput ; 35(6): 1367-1380, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-33169311

RESUMEN

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.


Asunto(s)
Procedimientos Quirúrgicos Cardíacos , Espectroscopía Infrarroja Corta , Animales , Oximetría , Oxígeno , Consumo de Oxígeno , Saturación de Oxígeno , Porcinos
13.
Cancer Res ; 81(4): 1101-1110, 2021 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-33318038

RESUMEN

While opioids constitute the major component of perioperative analgesic regimens for surgery in general, a variety of evidence points to an association between perioperative opioid exposure and longer term oncologic outcomes. The mechanistic details underlying these effects are not well understood. In this study, we focused on clear cell renal cell carcinoma (ccRCC) and utilized RNA sequencing and outcome data from both The Cancer Genome Atlas, as well as a local patient cohort to identify survival-associated gene coexpression networks. We then projected drug-induced transcriptional profiles from in vitro cancer cells to predict drug effects on these networks and recurrence-free, cancer-specific, and overall survival. The opioid receptor agonist, leu-enkephalin, was predicted to have antisurvival effects in ccRCC, primarily through Th2 immune- and NRF2-dependent macrophage networks. Conversely, the antagonist, naloxone, was predicted to have prosurvival effects, primarily through angiogenesis, fatty acid metabolism, and hemopoesis pathways. Eight coexpression networks associated with survival endpoints in ccRCC were identified, and master regulators of the transition from the normal to disease state were inferred, a number of which are linked to opioid pathways. These results are the first to suggest a mechanism for opioid effects on cancer outcomes through modulation of survival-associated coexpression networks. While we focus on ccRCC, this methodology may be employed to predict opioid effects on other cancer types and to personalize analgesic regimens in patients with cancer for optimal outcomes. SIGNIFICANCE: This study suggests a possible molecular mechanism for opioid effects on cancer outcomes generally, with implications for personalization of analgesic regimens.


Asunto(s)
Analgésicos Opioides/farmacología , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/mortalidad , Redes Reguladoras de Genes , Neoplasias Renales/genética , Neoplasias Renales/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Renales/diagnóstico , Carcinoma de Células Renales/patología , Estudios de Casos y Controles , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Estudios de Cohortes , Epistasis Genética/efectos de los fármacos , Epistasis Genética/fisiología , Femenino , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Redes Reguladoras de Genes/efectos de los fármacos , Humanos , Neoplasias Renales/diagnóstico , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Mortalidad , Pronóstico , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética , Análisis de Supervivencia
14.
Br J Anaesth ; 126(2): 367-376, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33220939

RESUMEN

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.


Asunto(s)
Analgésicos Opioides/administración & dosificación , Cuidados Intraoperatorios , Mastectomía , Recurrencia Local de Neoplasia/prevención & control , Receptores Opioides/agonistas , Neoplasias de la Mama Triple Negativas/cirugía , Analgésicos Opioides/efectos adversos , Bases de Datos Factuales , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Humanos , Cuidados Intraoperatorios/efectos adversos , Cuidados Intraoperatorios/mortalidad , Mastectomía/efectos adversos , Mastectomía/mortalidad , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Receptores Opioides/genética , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/mortalidad , Microambiente Tumoral
15.
J Cardiothorac Vasc Anesth ; 35(2): 571-577, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32967792

RESUMEN

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.


Asunto(s)
Anestésicos , Taponamiento Cardíaco , Neoplasias , Derrame Pericárdico , Humanos , Neoplasias/complicaciones , Técnicas de Ventana Pericárdica , Estudios Retrospectivos
16.
J Med Syst ; 44(11): 189, 2020 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-32964363

RESUMEN

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.


Asunto(s)
Anestesia , Anestesiología , Adulto , Humanos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & control , Mejoramiento de la Calidad , Estudios Retrospectivos
19.
Anesth Analg ; 131(1): 16-23, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32543802

RESUMEN

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.


Asunto(s)
Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/terapia , Neoplasias/complicaciones , Neoplasias/terapia , Neumonía Viral/complicaciones , Neumonía Viral/terapia , COVID-19 , Brotes de Enfermedades , Humanos , Pandemias , Manejo de Atención al Paciente
20.
Anesthesiol Clin ; 38(2): 311-326, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32336386

RESUMEN

With a shift in the cultural, political, and social climate surrounding gender and gender identity, an increase in the acceptance and visibility of transgender individuals is expected. Anesthesiologists are thus more likely to encounter transgender and gender nonconforming patients in the perioperative setting. Anesthesiologists need to acquire an in-depth understanding of the transgender patient's medical and psychosocial needs. A thoughtful approach throughout the entirety of the perioperative period is key to the successful management of the transgender patient. This review provides anesthesiologists with a culturally relevant and evidence-based approach to transgender patients during the preoperative, intraoperative, and postoperative periods.


Asunto(s)
Atención Perioperativa , Personas Transgénero , Anestesiólogos , Femenino , Identidad de Género , Humanos , Cuidados Intraoperatorios , Masculino , Examen Físico , Cuidados Posoperatorios , Medición de Riesgo
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