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INTRODUCTION: A key simulation component is its capability to elicit physiological changes, improving recall. The primary aim was to determine whether parasympathetic responses to head-mounted display simulations (HMDs) were noninferior to in-person simulations. The secondary aims explored sympathetic and affective responses and learning effectiveness. METHODS: The authors conducted a noninferiority trial. Hospital providers who did not use chronotropic medications, have motion sickness, or have seizures were included. The authors randomized participants to in-person or HMD simulation. Biometric sensors collected respiratory sinus arrhythmia and skin conductance levels to measure parasympathetic and sympathetic states at baseline, during, and after the simulation. Affect was measured using a schedule. The authors measured 3-month recall of learning points and used split-plot analysis of variance and Mann-Whitney U tests to analyze. RESULTS: One hundred fifteen participants qualified, and the authors analyzed 56 in each group. Both groups experienced a significant change in mean respiratory sinus arrhythmia from baseline to during and from during to afterward. The difference of change between the groups from baseline to during was 0.134 (95% confidence interval = 0.142 to 0.410, P = 0.339). The difference of change from during the simulation to after was -0.060 (95% confidence interval = -0.337 to 0.217, P = 0.670). Noninferiority was not established for either period. Sympathetic arousal did not occur in either group. Noninferiority was not established for the changes in affect that were demonstrated. The mean scores of teaching effectiveness and achievement scores were not different. CONCLUSIONS: Although a parasympathetic and affective response to the video simulation on an HMD did occur, it was not discernibly noninferior to in-person in this study.
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Emociones , Simulación por Computador , HumanosRESUMEN
BACKGROUND: With a new generation of affordable portable virtual reality (VR), clinicians are discovering more utility for VR, while also identifying opportunities for improvement, such as the inability to reorient the horizon line during repositioning or transport, or modulate cognitive load in real time. AIM: At our institution, this lack of functionality prohibited or decreased VR usage in some clinical scenarios such as dressing changes with dynamic positioning. The purpose of this brief report is to describe the development and use of a VR application that is optimized for the healthcare setting and report historical effects of patients who utilized VR as supplement to Child Life procedures. Eligible affects per chart review included Happy, Relaxed, Anxious, Distressed, Unable to Assess. MATERIALS AND METHODS: Given the need for real-time reorientation and cognitive load modulation, we created the Space Pups™ VR application. The experience was launched as part of the Stanford Chariot Program in the summer of 2017, and its usage was tracked through the electronic medical record and a VR application dashboard. Chart review was queried from 3 January 2018 to 9 August 2021 for pediatric patients who used VR with real-time reorientation and cognitive load modulation as a supplement to their Child Life interventions. RESULTS: The Space Pups™ experience has been successfully used in a variety of settings, including perioperative care, vascular access, wound care, and ENT clinic, a total of 1696 times. Patients ranged from 6 years to 18-year old, with no reports of side effects. Significant results (P<0.001) were observed pre- and post-VR use for affect improvements in Happy, Relaxed, and Anxious, but not for Distressed. CONCLUSIONS: The ability to reorient VR experiences in real time has increased functionality where other applications have failed. RELEVANCE FOR PATIENTS: While more studies are needed to quantify the anxiolytic and pain-reducing effect of Space Pups™, our report demonstrates the feasibility of this VR experience as a non-pharmacological modality to safely increase patient cooperation in a wide variety of clinical settings.
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Insuflación , Manejo de la Vía Aérea , Broncoscopía , Dióxido de Carbono , Niño , Humanos , Proyectos Piloto , Estudios ProspectivosRESUMEN
Over the past couple of centuries, the training of American physicians, and anesthesiologists in particular, has undergone a radical transformation. The revolution of medical training has been and continues to be fueled by insights from learning theorists. In this historical review, we discuss the origins of American medical education in the 1700s and continue through the centuries illustrating the impact of learning theories on the education and training of anesthesiologists. In particular, we explore the impact of learning theories of the 1800s and the adult-centered teaching strategies of the 1900s. We also discuss the role of learning theories in molding medical education in the modern technological age.
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AIMS: The HTC VIVE virtual reality (VR) system is a potential tool for collecting kinematic data during inpatient and outpatient physical therapy (PT). When validated against research-grade systems, the VIVE has a reported translational error between 1.7 mm-2.0 cm. Our purpose was to portabilize the VIVE for room to room PT and validate the motion tracking software. METHODS: The VIVE was configured on a mobile cart. To validate the motion tracking software, the VIVE sensors (motion tracker, controller, headset) were mounted on a rigid linear track and driven through 10, one-meter translations in the X, Y, and Z axes. RESULTS: The mean translational error for all three sensors was below 4.9 cm. While error is greater than that reported for research-grade systems, motion tracking software on the portable VIVE unit appears to be a valid means of tracking aggregate movement. CONCLUSION: Some therapy may require more precise measurements, however, the advantages of portability and accessibility to patients may outweigh the limitation of reduced precision.
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The requisites for protein translation in T cells are poorly understood and how translation shapes the antitumor efficacy of T cells is unknown. Here we demonstrated that IL15-conditioned T cells were primed by the metabolic energy sensor AMP-activated protein kinase to undergo diminished translation relative to effector T cells. However, we showed that IL15-conditioned T cells exhibited a remarkable capacity to enhance their protein translation in tumors, which effector T cells were unable to duplicate. Studying the modulation of translation for applications in cancer immunotherapy revealed that direct ex vivo pharmacologic inhibition of translation elongation primed robust T-cell antitumor immunity. Our work elucidates that altering protein translation in CD8+ T cells can shape their antitumor capability.
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Linfocitos T CD8-positivos/inmunología , Inmunoterapia/métodos , Activación de Linfocitos/inmunología , Neoplasias/inmunología , Factor 2 de Elongación Peptídica/metabolismo , Biosíntesis de Proteínas , Animales , Línea Celular Tumoral , Técnicas de Cocultivo , Modelos Animales de Enfermedad , Femenino , Interleucina-15/metabolismo , Ratones , Ratones Endogámicos C57BL , Neoplasias/metabolismo , Neoplasias/terapiaRESUMEN
Effective cancer therapies simultaneously restrict tumor cell growth and improve anti-tumor immune responses. Targeting redox-dependent protein folding enzymes within the endoplasmic reticulum (ER) is an alternative approach to activation of the unfolded protein response (UPR) and a novel therapeutic platform to induce malignant cell death. E64FC26 is a recently identified protein disulfide isomerase (PDI) inhibitor that activates the UPR, oxidative stress, and apoptosis in tumor cells, but not normal cell types. Given that targeting cellular redox homeostasis is a strategy to augment T cell tumor control, we tested the effect of E64FC26 on healthy and oncogenic T cells. In stark contrast to the pro-UPR and pro-death effects we observed in malignant T cells, we found that E64FC26 improved viability and limited the UPR in healthy T cells. E64FC26 treatment also diminished oxidative stress and decreased global PDI expression in normal T cells. Oxidative stress and cell death are limited in memory T cells and we found that PDI inhibition promoted memory traits and reshaped T cell metabolism. Using adoptive transfer of tumor antigen-specific CD8 T cells, we demonstrate that T cells activated and expanded in the presence of E64FC26 control tumor growth better than vehicle-matched controls. Our data indicate that PDI inhibitors are a new class of drug that may dually inhibit tumor cell growth and improve T cell tumor control.
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Estrés del Retículo Endoplásmico , Inmunoterapia Adoptiva , Neoplasias/etiología , Neoplasias/metabolismo , Proteína Disulfuro Isomerasas/genética , Linfocitos T/inmunología , Linfocitos T/metabolismo , Animales , Línea Celular , Supervivencia Celular/genética , Modelos Animales de Enfermedad , Inmunoterapia Adoptiva/métodos , Interleucina-15/metabolismo , Melanoma Experimental , Ratones , Ratones Transgénicos , Neoplasias/patología , Neoplasias/terapia , Oxidación-Reducción , Estrés Oxidativo , Proteína Disulfuro Isomerasas/antagonistas & inhibidores , Proteína Disulfuro Isomerasas/metabolismo , Respuesta de Proteína DesplegadaRESUMEN
PURPOSE OF REVIEW: Anesthesia for cardiac surgery has traditionally utilized high-dose opioids to blunt the sympathetic response to surgery. However, recent data suggest that opioids prolong postoperative intubation, leading to increased morbidity. Given the increased risk of opioid dependency after in-hospital exposure to opioids, coupled with an increase in morbidity, regional techniques offer an adjunct for perioperative analgesia. The aim of this review is to describe conventional and emerging regional techniques for cardiac surgery. RECENT FINDINGS: Well-studied techniques such as thoracic epidurals and paravertebral blocks are relatively low risk despite lack of widespread adoption. Benefits include reduced opioid exposure after paravertebral blocks and reduced risk of perioperative myocardial infarction after epidurals. To further lower the risk of epidural hematoma and pneumothorax, new regional techniques have been studied, including parasternal, pectoral, and erector spinae plane blocks. Because these are superficial compared with paravertebral and epidural blocks, they may have even lower risks of hematoma formation, whereas patients are anticoagulated on cardiopulmonary bypass. Efficacy data have been promising, although large and generalizable studies are lacking. SUMMARY: New regional techniques for cardiac surgery may be potent perioperative analgesic adjuncts, but well-designed studies are needed to quantify the effectiveness and safety of these blocks.
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Analgesia/métodos , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Bloqueo Nervioso/métodos , Dolor Postoperatorio/terapia , Atención Perioperativa/métodos , Analgesia/efectos adversos , Analgésicos no Narcóticos/administración & dosificación , Analgésicos Opioides/efectos adversos , Anestésicos Locales/administración & dosificación , Anestésicos Locales/efectos adversos , Humanos , Bloqueo Nervioso/efectos adversos , Epidemia de Opioides/etiología , Epidemia de Opioides/prevención & control , Dolor Postoperatorio/etiología , Atención Perioperativa/efectos adversos , Resultado del TratamientoRESUMEN
Tumor antigen-specific T cells rapidly lose energy and effector function in tumors. The cellular mechanisms by which energy loss and inhibition of effector function occur in tumor-infiltrating lymphocytes (TILs) are ill-defined, and methods to identify tumor antigen-specific TILs that experience such stress are unknown. Processes upstream of the mitochondria guide cell-intrinsic energy depletion. We hypothesized that a mechanism of T-cell-intrinsic energy consumption was the process of oxidative protein folding and disulfide bond formation that takes place in the endoplasmic reticulum (ER) guided by protein kinase R-like endoplasmic reticulum kinase (PERK) and downstream PERK axis target ER oxidoreductase 1 (ERO1α). To test this hypothesis, we created TCR transgenic mice with a T-cell-specific PERK gene deletion (OT1 + Lckcre+ PERK f/f , PERK KO). We found that PERK KO and T cells that were pharmacologically inhibited by PERK or ERO1α maintained reserve energy and exhibited a protein profile consistent with reduced oxidative stress. These T-cell groups displayed superior tumor control compared with T effectors. We identified a biomarker of ER-induced mitochondrial exhaustion in T cells as mitochondrial reactive oxygen species (mtROS), and found that PD-1+ tumor antigen-specific CD8+ TILs express mtROS. In vivo treatment with a PERK inhibitor abrogated mtROS in PD-1+ CD8+ TILs and bolstered CD8+ TIL viability. Combination therapy enabled 100% survival and 71% tumor clearance in a sarcoma mouse model. Our data identify the ER as a regulator of T-cell energetics and indicate that ER elements are effective targets to improve cancer immunotherapy.
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Linfocitos T CD8-positivos/metabolismo , Estrés del Retículo Endoplásmico/fisiología , Linfocitos Infiltrantes de Tumor/metabolismo , Mitocondrias/metabolismo , Animales , Linfocitos T CD8-positivos/inmunología , Retículo Endoplásmico/genética , Retículo Endoplásmico/metabolismo , Técnicas de Inactivación de Genes , Humanos , Memoria Inmunológica , Inmunoterapia , Linfocitos Infiltrantes de Tumor/inmunología , Ratones , Oxidorreductasas/antagonistas & inhibidores , Oxidorreductasas/metabolismo , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Sarcoma/patología , Sarcoma/terapia , Transducción de Señal , eIF-2 Quinasa/antagonistas & inhibidores , eIF-2 Quinasa/genética , eIF-2 Quinasa/metabolismoRESUMEN
OBJECTIVES: To characterize alterations in Spanish language medical interpretation during pediatric critical care family meetings. DESIGN: Descriptive, observational study using verbatim transcripts of nine PICU family meetings conducted with in-person, hospital-employed interpreters. SETTING: A single, university-based, tertiary children's hospital. SUBJECTS: Medical staff, family members, ancillary staff, and interpreters. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Interpreted speech was compared with original clinician or family speech using the qualitative research methods of directed content analysis and thematic analysis. Alterations occurred in 56% of interpreted utterances and included additions, omissions, substitutions, editorializations, answering for the patient/clinician, confessions, and patient advocacy. Longer utterances were associated with more alterations. CONCLUSIONS: To minimize interpreter alterations during family meetings, physicians should speak in short utterances (fewer than 20 words) and ask interpreters to interrupt in order to facilitate accurate interpretation. Because alterations occur, physicians may also regularly attempt to assess the family's understanding.