Space surgery: a SAGES' white paper.

BACKGROUND: Space travel is experiencing a renaissance with expanding commercial and international efforts. Space surgery will have growing relevance as mission frequency and distances increase beyond low Earth orbit. METHODS: This white paper from the SAGES Space Surgery Task Force raises awareness among the SAGES membership regarding the challenges and opportunities surrounding this emerging field that anticipates surgical care in the most extreme, austere environments. RESULTS: Innovation in technology and preventive medicine principles will enhance the effectiveness of space surgical care when the need arises. The impact of advancements in space and terrestrial medicine to support space exploration indicates the need for a surgeon to oversee medical/surgical invasive treatment to ensure astronaut health and mission success. Advanced technology, including semi- and autonomous robotic systems, may be a preferred way to deliver this care in the foreseeable future. There is currently a need to develop training curricula and flight-compatible supplies and technology for physicians that deliver surgical care to this special patient population. The protocols and technology developed to address the unique challenges of space travel will provide value for care in space as well as in extreme, austere terrestrial environments on Earth. CONCLUSION: Space surgery will continue to evolve as commercial and government programs explore further into space. The SAGES Space Surgery Task Force is favorably positioned to significantly contribute to addressing some capability gaps in delivering surgical care in space.

Opioid Prescribing After Discharge in a Previously Mechanically Ventilated, Opioid-Naïve Cohort.

BACKGROUND: Opioids are utilized for pain management during and after mechanical ventilation in the intensive care unit (ICU). OBJECTIVE: The purpose of this study was to determine the percentage of potentially unnecessary opioid prescriptions on discharge in previously opioid-naïve patients. METHODS: This retrospective cohort study included mechanically ventilated, opioid-naïve ICU patients who received opioids. The primary outcome of this study was the discrepancy between the amounts of opioids prescribed at discharge versus those likely required based on actual 24-hour prehospital discharge opioid requirements. RESULTS: A total of 71 patients were included. Of these, 63.3% (n = 45) of discharge prescriptions were in alignment with 24-hour predischarge requirements, and 36.7% (n = 26) of discharge prescriptions were in excess of calculated predischarge requirements. At discharge, 57.7% (n = 41) of patients received a nonopioid analgesic. Multivariable linear regression revealed that cardiothoracic ICU admission was associated with an increased risk of inappropriate discharge opioid prescribing, whereas a shorter duration of inpatient oral opioid therapy decreased risk of inappropriate discharge prescribing. CONCLUSION AND RELEVANCE: Opioid prescribing for previously mechanically ventilated patients warrants improvement as a part of the discharge planning process. Application of these data may aid in the reduction of opioid overprescribing at discharge after an ICU stay.

Pharmacist Interventions in a Palliative PLUS Program at a Veterans Affairs Medical Center.

Background: Palliative PLUS (PP) at the Minneapolis Veterans Affairs Health Care System (MVAHCS) is an interdisciplinary team that seeks to improve veteran access to palliative and hospice resources. Palliative care pharmacists were incorporated to increase patient access to palliative specialties. Objective: To identify and categorize pharmacist interventions within an outpatient PP team at the MVAHCS. Methods: This quality improvement project was a retrospective analysis of the electronic health record. Results: A total of 84 patients were participating in the PP program over 13 months. Among those patients, 25 had pharmacist involvement and a total of 56 interventions were identified. Of those interventions, 29 (51.8%) were direct interventions and 27 (48.2%) were curbside consults. Most interventions involved medication counseling and medication adherence. Conclusion: Pharmacists made an impact on the PP team through direct patient interventions involving medication counseling and aided the interdisciplinary team by facilitating patient medication adherence.

Asbestos-induced alveolar epithelial cell apoptosis. The role of endoplasmic reticulum stress response.

Asbestos exposure results in pulmonary fibrosis (asbestosis) and malignancies (bronchogenic lung cancer and mesothelioma) by mechanisms that are not fully understood. Alveolar epithelial cell (AEC) apoptosis is important in the development of pulmonary fibrosis after exposure to an array of toxins, including asbestos. An endoplasmic reticulum (ER) stress response and mitochondria-regulated (intrinsic) apoptosis occur in AECs of patients with idiopathic pulmonary fibrosis, a disease with similarities to asbestosis. Asbestos induces AEC intrinsic apoptosis, but the role of the ER is unclear. The objective of this study was to determine whether asbestos causes an AEC ER stress response that promotes apoptosis. Using human A549 and rat primary isolated alveolar type II cells, amosite asbestos fibers increased AEC mRNA and protein expression of ER stress proteins involved in the unfolded protein response, such as inositol-requiring kinase (IRE) 1 and X-box-binding protein-1, as well as ER Ca²(2+) release ,as assessed by a FURA-2 assay. Eukarion-134, a superoxide dismutase/catalase mimetic, as well as overexpression of Bcl-XL in A549 cells each attenuate asbestos-induced AEC ER stress (IRE-1 and X-box-binding protein-1 protein expression; ER Ca²(2+) release) and apoptosis. Thapsigargin, a known ER stress inducer, augments AEC apoptosis, and eukarion-134 or Bcl-XL overexpression are protective. Finally, 4-phenylbutyric acid, a chemical chaperone that attenuates ER stress, blocks asbestos- and thapsigargin-induced AEC IRE-1 protein expression, but does not reduce ER Ca²(2+) release or apoptosis. These results show that asbestos triggers an AEC ER stress response and subsequent intrinsic apoptosis that is mediated in part by ER Ca²(2+) release.

Use of Cannabis for Agitation in Patients With Dementia.

Studies have reported changes in the endocannabinoid system in the brain of patients with Alzheimer's disease (AD), playing a role in the pathophysiology of AD. Cannabinoids have been shown to have neuroprotective properties, reduce neuroinflammation, and enhance neurogenesis. Evidence suggests that the utilization of marijuana products containing both tetrahydrocannabinol (THC) and cannabidiol (CBD) or CBD alone have been effective and safe for use in older people with agitation associated with dementia. A review in 2017 summarized positive findings for therapeutic benefits of cannabinoids in agitation of AD and dementia, but there was no definitive conclusion because of varying cannabinoid products. Cannabinoids were shown to be well tolerated, with few short-term side effects. This differs from first-line medications utilized for dementia behaviors, which can have unwanted side effects. Further research regarding the safety, efficacy, and variability of these products in older people is needed.

Evaluation of the utricular function with the virtual-subject visual vertical system: comparison with ocular vestibular-evoked myogenic potentials.

Introduction: The subjective visual vertical (SVV) is the most frequently assessed modality of verticality perception and has been measured in a variety of clinical situations, including peripheral vestibular lesions.Aim: The main objectives are (1) to collect normative data of Virtual SVV™ from healthy subjects, and (2) to study the correlation between Virtual SVV™ and ocular vestibular-evoked myogenic potentials (o-VEMP) on healthy subjects.Materials and methods: Forty-three healthy subjects were recruited. Air conduction (AC)-elicited oVEMPs and bone conduction (BC)-elicited oVEMPs were measured. BC stimuli were produced with a RadioEar B-81 High Output Bone Transducer. Virtual SVV™ were also measured.Results: Virtual SVV™ data from our healthy subjects were consistent with previously published normative SVV data. Normal Virtual SVV™ data did not correlate with normal AC-elicited and BC-elicited oVEMPs.Conclusions: Virtual SVV™ data from our healthy subjects were consistent with previously published normative SVV data. Virtual SVV™ data from our 43 health subjects only had weak correlation with c-VEMP, AC-elicited and BC-elicited oVEMPs. These data serve as a baseline for a future study of patients with unilateral utricular dysfunction.Significance: The Virtual SVV™ can be an attractive substitute for traditional SVV in clinical settings.

Vicinal functionalization of propiolate esters via a tandem catalytic carbocupration-Mukaiyama aldol reaction sequence.

The vicinal functionalization of propiolate esters via a tandem catalytic carbocupration-Mukaiyama aldol reaction sequence has been investigated. It has been shown that catalyst loadings as low as 8 mol % readily allow for good yields and excellent diastereoselectivities (>20:1) for a series of Grignard reagents and aldehydes.

A highly stereoselective TMSOTf-mediated catalytic carbocupration of alkynoates.

The TMSOTf-mediated catalytic carbocupration of ynoates has been investigated. It has been shown that catalyst loadings as low as 5 mol % readily allow for high yields and diastereoselectivities for a series of aromatic Grignard reagents. In addition, we have been successful in vicinally functionalizing 1a via initial TMSOTf-mediated catalytic carbocupration followed by a secondary electrophilic capture of the TMS allenoate intermediate.

Modeling the Effect of the Aryl Hydrocarbon Receptor on Transplant Immunity.

BACKGROUND: Exposure to pollutants through inhalation is a risk factor for lung diseases including cancer, asthma, and lung transplant rejection, but knowledge of the effects of inhaled pollutants on pathologies outside of the lung is limited. METHODS: Using the minor-mismatched model of male C57BL/6J (B6) to female B6 skin grafts, recipient mice were treated with an inhaled urban dust particle sample every 3 days before and after grafting. Graft survival time was determined, and analysis of the resulting immune response was performed at time before rejection. RESULTS: Significant prolongation of male skin grafts occurred in recipient female mice treated with urban dust particles compared with controls and was found to be dependent on aryl hydrocarbon receptor (AHR) expression in the recipient mouse. T cell responses to the male histocompatibility antigen (H-Y) Dby were not altered by exposure to pollutants. A reduction in the frequency of IFNγ-producing CD4 T cells infiltrating the graft on day 7 posttransplant was observed. Flow cytometry analysis revealed that AHR expression is upregulated in IFNγ-producing CD4 T cells during immune responses in vitro and in vivo. CONCLUSIONS: Surprisingly, inhalation of a pollutant standard was found to prolong graft survival in a minor-mismatched skin graft model in an AHR-dependent manner. One possible mechanism may be an effect on IFNγ-producing CD4 T cells responding to donor antigen. The increased expression of AHR in this CD4 T cell subset suggests that AHR ligands within the particulate matter may be directly affecting the type 1 T helper cell response in this model.

Molecular mechanisms of asbestos-induced lung epithelial cell apoptosis.

Asbestos causes pulmonary fibrosis (asbestosis) and malignancies (bronchogenic lung cancer and mesothelioma) by mechanisms that are not fully elucidated. Accumulating evidence show that alveolar epithelial cell (AEC) apoptosis is a crucial initiating and perpetuating event in the development of pulmonary fibrosis following exposure to a wide variety of noxious stimuli, including asbestos. We review the important molecular mechanisms underlying asbestos-induced AEC apoptosis. Specifically, we focus on the role of asbestos in augmenting AEC apoptosis by the mitochondria- and p53-regulated death pathways that result from the production of iron-derived reactive oxygen species (ROS) and DNA damage. We summarize emerging evidence implicating the endoplasmic reticulum (ER) stress response in AEC apoptosis in patients with idiopathic pulmonary fibrosis (IPF), a disease with similarities to asbestosis. Finally, we discuss a recent finding that a mitochondrial oxidative DNA repair enzyme (8-oxoguanine DNA glycosylase; Ogg1) acts as a mitochondrial aconitase chaperone protein to prevent oxidant (asbestos and H(2)O(2))-induced AEC mitochondrial dysfunction and intrinsic apoptosis. The coupling of mitochondrial Ogg1 to mitochondrial aconitase is a novel mechanism linking metabolism to mitochondrial DNA that may be important in the pathophysiologic events resulting in oxidant-induced toxicity as seen in tumors, aging, and respiratory disorders (e.g. asbestosis, IPF). Collectively, these studies are illuminating the molecular basis of AEC apoptosis following asbestos exposure that may prove useful for developing novel therapeutic strategies. Importantly, the asbestos paradigm is elucidating pathophysiologic insights into other more common pulmonary diseases, such as IPF and lung cancer, for which better therapy is required.