Re-resection of Microscopically Positive Margins Found on Intraoperative Frozen Section Analysis Does Not Result in a Survival Benefit in Patients Undergoing Surgery and Intraoperative Radiation Therapy for Locally Recurrent Rectal Cancer
BACKGROUND: Intraoperative frozen-section analysis provides real-time margin resection status that can guide intraoperative decisions made by the surgeon and radiation oncologist. For patients with locally recurrent rectal cancer undergoing surgery and intraoperative radiation therapy, intraoperative re-resection of positive margins to achieve negative margins is common practice. OBJECTIVE: This study aimed to assess whether re-resection of positive margins found on intraoperative frozen-section analysis improves oncologic outcomes. DESIGN: This is a retrospective cohort study. SETTINGS: This study was an analysis of a prospectively maintained multicenter database. PATIENTS: All patients who underwent surgical resection of locally recurrent rectal cancer with intraoperative radiation therapy between 2000 and 2015 were included and followed for 5 years. Three groups were compared: initial R0 resection, initial R1 converted to R0 after re-resection, and initial R1 that remained R1 after re-resection. Grossly positive margin resections (R2) were excluded. MAIN OUTCOME MEASURES: The primary outcome measures were 5-year overall survival, recurrence-free survival, and local re-recurrence. RESULTS: A total of 267 patients were analyzed (initial R0 resection, n = 94; initial R1 converted to R0 after re-resection, n = 95; initial R1 that remained R1 after re-resection, n = 78). Overall survival was 4.4 years for initial R0 resection, 2.7 years for initial R1 converted to R0 after re-resection, and 2.9 years for initial R1 that remained R1 after re-resection (p = 0.01). Recurrence-free survival was 3.0 years for initial R0 resection and 1.8 years for both initial R1 converted to R0 after re-resection and initial R1 that remained R1 after re-resection (p ≤ 0.01). Overall survival did not differ for patients with R1 and re-resection R1 or R0 (p = 0.62). Recurrence-free survival and freedom from local re-recurrence did not differ between groups. LIMITATIONS: This study was limited by the heterogeneous patient population restricted to those receiving intraoperative radiation therapy. CONCLUSIONS: Re-resection of microscopically positive margins to obtain R0 status does not appear to provide a significant survival advantage or prevent local re-recurrence in patients undergoing surgery and intraoperative radiation therapy for locally recurrent rectal cancer. See Video Abstract at http://links.lww.com/DCR/B886. LA RE-RESECCIÓN DE LOS MÁRGENES MICROSCÓPICAMENTE POSITIVOS ENCONTRADOS DE MANERA INTRAOPERATORIA MEDIANTE LA TÉCNICA DE CRIOSECCIÓN, NO DA COMO RESULTADO UN BENEFICIO DE SUPERVIVENCIA EN PACIENTES SOMETIDOS A CIRUGÍA Y RADIOTERAPIA INTRAOPERATORIA PARA EL CÁNCER RECTAL LOCALMENTE RECIDIVANTE ANTECEDENTES: El análisis de la ténica de criosección para los margenes positivos encontrados de manera intraoperatoria proporciona el estado de la resección del margen en tiempo real que puede guiar las decisiones intraoperatorias tomadas por el cirujano y el oncólogo radioterapeuta. Para los pacientes con cáncer de recto localmente recurrente que se someten a cirugía y radioterapia intraoperatoria, la re-resección intraoperatoria de los márgenes positivos para lograr márgenes negativos es una práctica común. OBJETIVO: Evaluar si la re-resección de los márgenes positivos encontrados en el análisis de la ténica por criosecciónde manera intraoperatorios mejora los resultados oncológicos. DISEÑO: Estudio de cohorte retrospectivo. AJUSTES: Análisis de una base de datos multicéntrica mantenida de forma prospectiva. POBLACIÓN: Todos los pacientes que se sometieron a resección quirúrgica de cáncer de recto localmente recurrente con radioterapia intraoperatoria entre 2000 y 2015 fueron incluidos y seguidos durante 5 años. Se compararon tres grupos: resección inicial R0, R1 inicial convertido en R0 después de la re-resección y R1 inicial que permaneció como R1 después de la re-resección. Se excluyeron las resecciones de márgenes macroscópicamente positivos (R2). PRINCIPALES MEDIDAS DE RESULTADO: Supervivencia global a cinco años, supervivencia sin recidiva y recidiva local. RESULTADOS: Se analizaron un total de 267 pacientes (resección inicial R0 n = 94, R1 inicial convertido en R0 después de la re-resección n = 95, R1 inicial que permaneció como R1 después de la re-resección n = 78). La supervivencia global fue de 4,4 años para la resección inicial R0, 2,7 años para la R1 inicial convertida en R0 después de la re-resección y 2,9 años para la R1 inicial que permaneció como R1 después de la re-resección (p = 0,01). La supervivencia libre de recurrencia fue de 3,0 años para la resección inicial R0 y de 1,8 años para el R1 inicial convertido en R0 después de la re-resección y el R1 inicial que permaneció como R1 después de la re-resección (p ≤ 0,01). La supervivencia global no difirió para los pacientes con R1 y re-resección R1 o R0 (p = 0,62). La supervivencia libre de recurrencia y la ausencia de recurrencia local no difirieron entre los grupos. LIMITACIONES: Población de pacientes heterogénea, restringida a aquellos que reciben radioterapia intraoperatoria. CONCLUSIONES: La re-resección de los márgenes microscópicamente positivos para obtener el estado R0 no parece proporcionar una ventaja de supervivencia significativa o prevenir la recurrencia local en pacientes sometidos a cirugía y radioterapia intraoperatoria para el cáncer de recto localmente recurrente. Consulte Video Resumen en http://links.lww.com/DCR/B886. (Traducción—Dr. Daniel Guerra)
Immunological Aspects of AXL/GAS‐6 in the Context of Human Liver Regeneration
AXL and its corresponding ligand growth arrest–specific 6 (GAS‐6) are critically involved in hepatic immunomodulation and regenerative processes. Pleiotropic inhibitory effects on innate inflammatory responses might essentially involve the shift of macrophage phenotype from a pro‐inflammatory M1 to an anti‐inflammatory M2. We aimed to assess the relevance of the AXL/GAS‐6‐pathway in human liver regeneration and, consequently, its association with clinical outcome after hepatic resection. Soluble AXL (sAXL) and GAS‐6 levels were analyzed at preoperative and postoperative stages in 154 patients undergoing partial hepatectomy and correlated with clinical outcome. Perioperative dynamics of interleukin (IL)‐6, soluble tyrosine‐protein kinase MER (sMerTK), soluble CD163 (sCD163), and cytokeratin (CK) 18 were assessed to reflect pathophysiological processes. Preoperatively elevated sAXL and GAS‐6 levels predicted postoperative liver dysfunction (area under the curve = 0.721 and 0.722; P < 0.005) and worse clinical outcome. These patients failed to respond with an immediate increase of sAXL and GAS‐6 upon induction of liver regeneration. Abolished AXL pathway response resulted in a restricted increase of sCD163, suggesting a disrupted phenotypical switch to regeneratory M2 macrophages. No association with sMerTK was observed. Concomitantly, a distinct association of IL‐6 levels with an absent increase of AXL/GAS‐6 signaling indicated pronounced postoperative inflammation. This was further supported by increased intrahepatic secondary necrosis as reflected by CK18M65. sAXL and GAS‐6 represent not only potent and easily accessible preoperative biomarkers for the postoperative outcome but also AXL/GAS‐6 signaling might be of critical relevance in human liver regeneration. Refractory AXL/GAS‐6 signaling, due to chronic overactivation/stimulation in the context of underlying liver disease, appears to abolish their immediate release following induction of liver regeneration, causing overwhelming immune activation, presumably via intrahepatic immune regulation.
Emergent and Urgent Surgery for Ulcerative Colitis in the United States in the Minimally Invasive and Biologic Era
BACKGROUND: Although the overall adoption of minimally invasive surgery in the nonemergent management of ulcerative colitis is established, little is known about its utilization in emergency settings. OBJECTIVE: The goal of this study was to assess rates of urgent and emergent surgery over time in the era of emerging biologic therapies and to highlight the current practice in the United States regarding the utilization of minimally invasive surgery for urgent and emergent indications for ulcerative colitis. DESIGN: This was a retrospective analysis study. SETTINGS: Data were collected from the American College of Surgeons National Quality Improvement Program database. PATIENTS: All adult patients who underwent emergent or urgent colectomy for ulcerative colitis were included. MAIN OUTCOME MEASURES: Rates of emergency operations over time and utilization trends of minimally invasive surgery in urgent and emergent settings were assessed. Unadjusted and adjusted overall, surgical, and medical 30-day complication rates were compared between open and minimally invasive surgery. RESULTS: A total of 2219 patients were identified. Of those, 1515 patients (68.3%) underwent surgery in an urgent setting and 704 (31.7%) as an emergency. Emergent cases decreased over time (21% in 2006 to 8% in 2018; p < 0.0001). However, the rate of urgent surgeries has not significantly changed (42% in 2011 to 46% in 2018; p = 0.44). Minimally invasive surgery was offered to 70% of patients in the urgent group (1058/1515) and 22.6% of emergent indications (159/704). Overall, minimally invasive surgery was increasingly utilized over the study period in urgent (38% in 2011 to 71% in 2018; p < 0.0001) and emergent (0% in 2005 to 42% in 2018; p < 0.0001) groups. Compared to minimally invasive surgery, open surgery was associated with a higher risk of surgical, septic, and overall complications, and prolonged hospitalization. LIMITATIONS: This study was limited by its retrospective nature of the analysis. CONCLUSION: Based on a nationwide analysis from the United States, minimally invasive surgery has been increasingly and safely implemented for emergent and urgent indications for ulcerative colitis. Although the sum of emergent and urgent cases remained the same over the study period, emergency cases decreased significantly over the study period, which may be related to improved medical treatment options and a collaborative, specialized team approach. See Video Abstract at http://links.lww.com/DCR/B847. CIRUGÍA DE URGENCIA Y EMERGENCIA PARA LA COLITIS ULCEROSA EN LOS ESTADOS UNIDOS EN LA ERA MÍNIMAMENTE INVASIVA Y DE TERAPIA BIOLÓGICA ANTECEDENTES: Si bien se ha establecido la adopción generalizada de la cirugía mínimamente invasiva en el tratamiento electivo de la colitis ulcerosa, se sabe poco sobre su utilización en situaciones de emergencia. OBJETIVO: Evaluar las tasas de cirugía de urgencia a lo largo del tiempo en la era de las terapias biológicas emergentes y destacar la práctica actual en los Estados Unidos con respecto a la utilización de la cirugía mínimamente invasiva para las indicaciones de urgencia y emergencia de la colitis ulcerosa. DISEÑO: Análisis retrospectivo. AJUSTES: Base de datos del Programa Nacional de Mejoramiento de la Calidad del Colegio Americano de Cirujanos. PACIENTES: Todos los pacientes adultos que se sometieron a colectomía de emergencia o urgencia por colitis ulcerosa. MEDIDAS DE RESULTADO: Se evaluaron las tasas de operaciones de emergencia a lo largo del tiempo y las tendencias de utilización de la cirugía mínimamente invasiva en entornos de urgencia y emergencia. Se compararon las tasas de complicaciones generales, quirúrgicas y médicas de 30 días no ajustadas y ajustadas entre la cirugía abierta y la mínimamente invasiva. RESULTADOS: Se identificaron un total de 2.219 pacientes. De ellos, 1.515 pacientes (68,3%) fueron intervenidos de urgencia y 704 (31,7%) de emergencia. Los casos emergentes disminuyeron con el tiempo (21% en 2006 a 8% en 2018; p <0,0001). Sin embargo, la tasa de cirugías urgentes no ha cambiado significativamente (42% en 2011 a 46% en 2018, p = 0,44). Se ofreció cirugía mínimamente invasiva al 70% de los pacientes del grupo urgente (1.058 / 1.515) y al 22,6% de las emergencias (159/704). En general, la cirugía mínimamente invasiva se utilizó cada vez más durante el período de estudio en grupos urgentes (38% en 2011 a 71% en 2018; p <0,0001) y emergentes (0% en 2005 a 42% en 2018; p <0,0001). En comparación con la cirugía mínimamente invasiva, la cirugía abierta se asoció con un mayor riesgo de complicaciones generales, quirúrgicas, sépticas y hospitalización prolongada. LIMITACIONES: Carácter retrospectivo del análisis. CONCLUSIÓNES: Basado en un análisis nacional de los Estados Unidos, la cirugía mínimamente invasiva se ha implementado de manera creciente y segura para las indicaciones emergentes y urgentes de la colitis ulcerosa. Si bien la suma de casos emergentes y urgentes permaneció igual durante el período de estudio, los casos de emergencia disminuyeron significativamente, lo que puede estar relacionado con mejores opciones de tratamiento médico y un enfoque de equipo colaborativo y especializado. Consulte Video Resumen en http://links.lww.com/DCR/B847. (Traducción—Dr. Felipe Bellolio)
Oral Antibiotics Bowel Preparation Without Mechanical Preparation for Minimally Invasive Colorectal Surgeries: Current Practice and Future Prospects
BACKGROUND: The efficacy of preoperative oral antibiotics alone compared with mechanical and oral antibiotic bowel preparation in minimally invasive surgery is still a matter of debate. OBJECTIVE: This study aimed to assess the trend of surgical site infection rates in parallel to the utilization of bowel preparation modality over time for minimally invasive colorectal surgeries in the United States. DESIGN: This study is a retrospective analysis. SETTINGS: The American College of Surgeons National Surgical Quality Improvement Program database was the source of data for this study. PATIENTS: Adult patients who underwent elective colorectal surgery and reported bowel preparation modality were included. MAIN OUTCOME MEASURES: The primary outcomes measured were the trends and the comparison of surgical site infection rates for mutually exclusive groups according to the underlying disease (colorectal cancer, IBD, and diverticular disease) who underwent bowel preparation using oral antibiotics or combined mechanical and oral antibiotic bowel preparation. Patients who underwent rectal surgery were analyzed separately. RESULTS: A total of 30,939 patients were included. Of them, 12,417 (40%) had rectal resections. Over the 7-year study period, mechanical and oral antibiotic bowel preparation utilization increased from 29.3% in 2012 to 64.0% in 2018; p < 0.0001 at the expense of no preparation and mechanical bowel preparation alone. Similarly, oral antibiotics utilization increased from 2.3% in 2012 to 5.5% in 2018; p < 0.0001. For patients with colon cancer, patients who had oral antibiotics alone had higher superficial surgical site infection rates than patients who had combined mechanical and oral antibiotic bowel preparation (1.9% vs 1.1%; p = 0.043). Superficial, deep, and organ space surgical site infection rates were similar for all other comparative colon surgery groups (cancer, IBD, and diverticular disease). Patients with rectal cancer who had oral antibiotics had higher rates of deep surgical site infection (0.9% vs 0.1%; p = 0.004). However, superficial, deep, and organ space surgical site infection rates were similar for all other comparative rectal surgery groups. LIMITATIONS: This study was limited by the retrospective nature of the analysis. CONCLUSION: This study revealed widespread adoption of mechanical and oral antibiotic bowel preparation and increased adoption of oral antibiotics over the study period. Surgical site infection rates are similar from a clinical relevance standpoint among most comparative groups, questioning the systematic preoperative addition of mechanical bowel preparation to oral antibiotics alone in all patients for minimally invasive colorectal surgery. See Video Abstract at http://links.lww.com/DCR/B828. PREPARACIÓN INTESTINAL CON ANTIBIÓTICOS ORALES SIN PREPARACIÓN MECÁNICA EN CIRUGÍAS COLORRECTALES MÍNIMAMENTE INVASIVAS: PRÁCTICA ACTUAL Y PERSPECTIVAS FUTURAS ANTECEDENTES: La eficacia de los antibióticos orales preoperatorios solos en comparación con la preparación intestinal mecánica mas antibióticos orales en la cirugía mínimamente invasiva es un tema de debate que todavía esta en curso. OBJETIVO: Este estudio tuvo como objetivo evaluar la tendencia de las tasas de infección del sitio quirúrgico en relacion a la utilización de la modalidad de preparación intestinal a lo largo del tiempo en cirugías colorrectales mínimamente invasivas en los Estados Unidos. DISEÑO: Análisis retrospectivo. ENTORNO CLINICO: Base de datos del Programa Nacional de Mejoramiento de la Calidad Quirúrgica del Colegio Estadounidense de Cirujanos. PACIENTES: Pacientes adultos sometidos a cirugía colorrectal electiva y reportados con modalidad de preparación intestinal. PRINCIPALES MEDIDAS DE VALORACIÓN: Tendencias y comparacion de las tasas de infección del sitio quirúrgico para grupos mutuamente excluyentes según la enfermedad subyacente (cáncer colorrectal, enfermedad inflamatoria intestinal y enfermedad diverticular) que se sometieron a preparación intestinal usando antibióticos orales exclusivamente o preparación intestinal mecánica combinada con antibióticos orales. Los pacientes que se sometieron a cirugía rectal se analizaron por separado. RESULTADOS: Se incluyeron un total de 30.939 pacientes. De ellos, 12.417 (40%) se sometieron a resecciones rectales. Durante el período de estudio de siete años, la preparación mecánica del intestino y la utilización de antibióticos orales aumentó del 29,3% en 2012 al 64,0% en 2018; p < 0,0001 sobre la no preparación y de la preparación intestinal mecánica exclusivamente. De manera similar, la utilización de antibióticos orales ha aumentado del 2,3% en 2012 al 5,5% en 2018; p < 0,0001. Para los pacientes con cáncer de colon, los pacientes que recibieron antibióticos orales solos tuvieron mayores tasas de infección superficial del sitio quirúrgico en comparación con los pacientes que recibieron una preparación intestinal mecánica combinada con antibióticos orales (1,9% frente a 1,1%; p = 0,043). Las tasas de infección superficial, profundo del sitio quirúrgico y de los compartimientos intraabdominales fueron similares para todos los demás grupos de cirugía de colon (cáncer, enfermedad inflamatoria intestinal y enfermedad diverticular). Los pacientes con cáncer de recto que recibieron antibióticos orales tuvieron tasas más altas de infección profunda del sitio quirúrgico (0,9% frente a 0,1%; p = 0,004). Sin embargo, las tasas de infección del sitio quirúrgico superficial, profundo y de los compartimientos intraabdominales fueron similares comparativamente para todos los demás grupos de cirugía rectal. LIMITACIONES: Carácter retrospectivo del análisis. CONCLUSIONES: Este estudio reveló la adopción generalizada de preparación intestinal mecánica y antibióticos orales y una mayor aceptación de antibióticos orales durante el período de estudio. Las tasas de infección del sitio quirúrgico parecen ser similares desde un punto de vista de relevancia clínica entre la mayoría de los grupos comparados, lo que cuestiona la adición preoperatoria sistemática de preparación intestinal mecánica a antibióticos orales solos en todos los pacientes para cirugía colorrectal mínimamente invasiva. Consulte Video Resumen en http://links.lww.com/DCR/B828. (Traducción— Dr. Ingrid Melo)
Association Between Tumor Necrosis Factor Inhibitors and the Risk of Hospitalization or Death Among Patients With Immune-Mediated Inflammatory Disease and COVID-19
Aim: The aim of this study was to assess the implementation of an intraoperative standardized surgical site infection (SSI) prevention bundle. Methods: The multimodal, evidence-based care bundle included nine intraoperative items (antibiotic type, timing, and re-dosing; disinfection; induction temperature control > 36.5°; glove change; intra-cavity lavage; wound protection; and closure strategy). The bundle was applied to all consecutive patients undergoing colonic resections. The primary outcome, SSI, was independently assessed by the National Infection Surveillance Committee for up to 30 postoperative days. A historical, institutional pre-implementation control group (2012–2017) with an identical methodology was used for comparison. Findings: In total, 1516 patients were included, of which 1256 (82.8%) were in the control group and 260 (17.2%) were in the post-implementation group. After 2:1 propensity score matching, the groups were similar for all items (p > 0.05). Overall compliance with the care bundle was 77% (IQR 77–88). The lowest compliance rates were observed for temperature control (53% overall), intra-cavity lavage (64% overall), and wound protection and closure (68% and 63% in the SSI group, respectively). Surgical site infections were reported in 58 patients (22.2%) vs. 21.4% in the control group (p = 0.79). Infection rates were comparable throughout the Centers for Disease Control and Prevention (CDC) categories: superficial, 12 patients (4.5%) vs. 4.2%, p = 0.82; deep incisional, 10 patients (3.7%) vs. 5.1%, p = 0.34; organ space, 36 (14%) vs. 12.4%, p = 0.48. After propensity score matching, rates remained comparable throughout all comparisons (all p > 0.05). Conclusions: The implementation of an intraoperative standardized care bundle had no impact on SSI rates. This may be explained by insufficient compliance with the individual measures.
Pulmonary Open, Robotic, and Thoracoscopic Lobectomy (PORTaL) Study
Objective: The aim of this study was to analyze outcomes of open lobectomy (OL), VATS, and robotic-assisted lobectomy (RL). Summary Background Data: Robotic-assisted lobectomy has seen increasing adoption for treatment of early-stage lung cancer. Comparative data regarding these approaches is largely from single-institution case series or administrative datasets. Methods: Retrospective data was collected from 21 institutions from 2013 to 2019. All consecutive cases performed for clinical stage IA-IIIA lung cancer were included. Neoadjuvant cases were excluded. Propensity-score matching (1:1) was based on age, sex, race, smoking-status, FEV1%, Zubrod score, American Society of Anesthesiologists score, tumor size, and clinical T and N stage. Results: A total of 2391 RL, 2174 VATS, and 1156 OL cases were included. After propensity-score matching there were 885 pairs of RL vs OL, 1,711 pairs of RL vs VATS, and 952 pairs of VATS vs OL. Operative time for RL was shorter than VATS (P < 0.0001) and OL (P = 0.0004). Compared to OL, RL and VATS had less overall postoperative complications, shorter hospital stay (LOS), and lower transfusion rates (all P<0.02). Compared to VATS, RL had lower conversion rate (P<0.0001), shorter hospital stay (P<0.0001) and a lower postoperative transfusion rate (P =0.01). RL and VATS cohorts had comparable postoperative complication rates. In-hospital mortality was comparable between all groups. Conclusions: RL and VATS approaches were associated with favorable perioperative outcomes compared to OL. Robotic-assisted lobectomy was also associated with a reduced length of stay and decreased conversion rate when compared to VATS.
Telomerase and Pluripotency Factors Jointly Regulate Stemness in Pancreatic Cancer Stem Cells
To assess the role of telomerase activity and telomere length in pancreatic CSCs we used different CSC enrichment methods (CD133, ALDH, sphere formation) in primary patient-derived pancreatic cancer cells. We show that CSCs have higher telomerase activity and longer telomeres than bulk tumor cells. Inhibition of telomerase activity, using genetic knockdown or pharmacological inhibitor (BIBR1532), resulted in CSC marker depletion, abrogation of sphere formation in vitro and reduced tumorigenicity in vivo. Furthermore, we identify a positive feedback loop between stemness factors (NANOG, OCT3/4, SOX2, KLF4) and telomerase, which is essential for the self-renewal of CSCs. Disruption of the balance between telomerase activity and stemness factors eliminates CSCs via induction of DNA damage and apoptosis in primary patient-derived pancreatic cancer samples, opening future perspectives to avoid CSC-driven tumor relapse. In the present study, we demonstrate that telomerase regulation is critical for the “stemness” maintenance in pancreatic CSCs and examine the effects of telomerase inhibition as a potential treatment option of pancreatic cancer. This may significantly promote our understanding of PDAC tumor biology and may result in improved treatment for pancreatic cancer patients.
The Efficacy of Electrical Baroreflex Activation Therapy is Independent of Peripheral Chemoreceptor Modulation
Introduction Baroreflex activation through electrical carotid sinus stimulation has been developed for the treatment of patients with arterial hypertension not sufficiently responding to pharmacological therapy. Previous studies suggested that peripheral chemoreflex afferents located in proximity to carotid baroreceptors are tonically active in hypertensive patients and may inhibit baroreflex responses. Therefore, we hypothesized that peripheral chemoreflex activation attenuates the efficacy of electrical carotid sinus stimulation. Methods We screened 35 patients with an implanted electrical carotid sinus stimulator. Of those, 11 patients exhibited a consistent acute depressor response and were included in the study (7 men/4 women, age: 67±8 years, BMI: 31.6±5.2 kg/m 2 , 6±2 antihypertensive drug classes). We assessed responses to electrical baroreflex stimulation during normoxia, isocapnic hypoxia (SpO2: 79.0±1.5%), and hyperoxia (40% end‐tidal O2 fraction) by recording ECG, blood pressure (SBP), ventilation, SpO2, end‐tidal CO2 and O2 fractions, and muscle sympathetic nerve activity (MSNA). Results During normoxia, baroreflex activation reduced SBP from 164±27 to 151±25 mmHg (means±SD, p<0.001), HR from 64±13 to 61±13 bpm (p=0.002), and MSNA from 42±12 to 36±12 bursts/min (p=0.004). Hypoxia increased SBP 8±12 mmHg (p=0.057), HR 10±6 bpm (p<0.001), MSNA 7±7 bursts/min (p=0.031), and ventilation 10±7 l/min (p=0. 002). However, responses to electrical carotid sinus stimulation did not differ between hypoxic and hyperoxic conditions; SBP: −15±7 vs −14±8 mmHg (p=0.938), HR: −2±3 vs −2±2 bpm (p=0.701), and MSNA: −6±4 vs −4±3 bursts/min (p=0.531). Conclusion The main finding of our study is that moderate peripheral chemoreflex activation does not attenuate acute responses to electrical baroreflex activation therapy (BAT) in patients with resistant hypertension. These patients provide insight in human baroreflex physiology and baroreflex‐chemoreflex interactions that could not be gained otherwise. Support or Funding Information Financial support by Boston Scientific Corporation (St. Paul, MN, U.S.A.) This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .