Pseudomonas aeruginosa uses a complex type III secretion system to inject the toxins ExoS, ExoT, ExoU, and ExoY into the cytosol of target eukaryotic cells. This system is regulated by the exoenzyme ...S regulon and includes the transcriptional activator ExsA. Of the four toxins, ExoU is characterized as the major virulence factor responsible for alveolar epithelial injury in patients with P. aeruginosa pneumonia. Virulent strains of P. aeruginosa possess the exoU gene, whereas non-virulent strains lack this particular gene. The mechanism of virulence for the exoU+ genotype relies on the presence of a pathogenic gene cluster (PAPI-2) encoding exoU and its chaperone, spcU. The ExoU toxin has a patatin-like phospholipase domain in its N-terminal, exhibits phospholipase A2 activity, and requires a eukaryotic cell factor for activation. The C-terminal of ExoU has a ubiquitinylation mechanism of activation. This probably induces a structural change in enzymatic active sites required for phospholipase A2 activity. In P. aeruginosa clinical isolates, the exoU+ genotype correlates with a fluoroquinolone resistance phenotype. Additionally, poor clinical outcomes have been observed in patients with pneumonia caused by exoU+-fluoroquinolone-resistant isolates. Therefore, the potential exists to improve clinical outcomes in patients with P. aeruginosa pneumonia by identifying virulent and antimicrobial drug-resistant strains through exoU genotyping or ExoU protein phenotyping or both.
The convergence of multiple recent developments in health care information technology and monitoring devices has made possible the creation of remote patient surveillance systems that increase the ...timeliness and quality of patient care. More convenient, less invasive monitoring devices, including patches, wearables, and biosensors, now allow for continuous physiological data to be gleaned from patients in a variety of care settings across the perioperative experience. These data can be bound into a single data repository, creating so-called data lakes. The high volume and diversity of data in these repositories must be processed into standard formats that can be queried in real time. These data can then be used by sophisticated prediction algorithms currently under development, enabling the early recognition of patterns of clinical deterioration otherwise undetectable to humans. Improved predictions can reduce alarm fatigue. In addition, data are now automatically queriable on a real-time basis such that they can be fed back to clinicians in a time frame that allows for meaningful intervention. These advancements are key components of successful remote surveillance systems. Anesthesiologists have the opportunity to be at the forefront of remote surveillance in the care they provide in the operating room, postanesthesia care unit, and intensive care unit, while also expanding their scope to include high-risk preoperative and postoperative patients on the general care wards. These systems hold the promise of enabling anesthesiologists to detect and intervene upon changes in the clinical status of the patient before adverse events have occurred. Importantly, however, significant barriers still exist to the effective deployment of these technologies and their study in impacting patient outcomes. Studies demonstrating the impact of remote surveillance on patient outcomes are limited. Critical to the impact of the technology are strategies of implementation, including who should receive and respond to alerts and how they should respond. Moreover, the lack of cost-effectiveness data and the uncertainty of whether clinical activities surrounding these technologies will be financially reimbursed remain significant challenges to future scale and sustainability. This narrative review will discuss the evolving technical components of remote surveillance systems, the clinical use cases relevant to the anesthesiologist's practice, the existing evidence for their impact on patients, the barriers that exist to their effective implementation and study, and important considerations regarding sustainability and cost-effectiveness.
The role of cardiothoracic anesthesiology intensivists has expanded over the past few decades. Cardiothoracic anesthesiology intensivists are taking on larger roles in cardiac critical care ...specializing in cardiogenic shock and extracorporeal membrane oxygenation.
The convergence of multiple recent developments in health care information technology and monitoring devices has made possible the creation of remote patient surveillance systems that increase the ...timeliness and quality of patient care. More convenient, less invasive monitoring devices, including patches, wearables, and biosensors, now allow for continuous physiological data to be gleaned from patients in a variety of care settings across the perioperative experience. These data can be bound into a single data repository, creating so-called data lakes. The high volume and diversity of data in these repositories must be processed into standard formats that can be queried in real time. These data can then be used by sophisticated prediction algorithms currently under development, enabling the early recognition of patterns of clinical deterioration otherwise undetectable to humans. Improved predictions can reduce alarm fatigue. In addition, data are now automatically queriable on a real-time basis such that they can be fed back to clinicians in a time frame that allows for meaningful intervention. These advancements are key components of successful remote surveillance systems. Anesthesiologists have the opportunity to be at the forefront of remote surveillance in the care they provide in the operating room, postanesthesia care unit, and intensive care unit, while also expanding their scope to include high-risk preoperative and postoperative patients on the general care wards. These systems hold the promise of enabling anesthesiologists to detect and intervene upon changes in the clinical status of the patient before adverse events have occurred. Importantly, however, significant barriers still exist to the effective deployment of these technologies and their study in impacting patient outcomes. Studies demonstrating the impact of remote surveillance on patient outcomes are limited. Critical to the impact of the technology are strategies of implementation, including who should receive and respond to alerts and how they should respond. Moreover, the lack of cost-effectiveness data and the uncertainty of whether clinical activities surrounding these technologies will be financially reimbursed remain significant challenges to future scale and sustainability. This narrative review will discuss the evolving technical components of remote surveillance systems, the clinical use cases relevant to the anesthesiologist’s practice, the existing evidence for their impact on patients, the barriers that exist to their effective implementation and study, and important considerations regarding sustainability and cost-effectiveness.
Treatment with bone-marrow-derived mesenchymal stromal cells (MSCs) has shown benefits in preclinical models of acute respiratory distress syndrome (ARDS). Safety has not been established for ...administration of MSCs in critically ill patients with ARDS. We did a phase 2a trial to assess safety after administration of MSCs to patients with moderate to severe ARDS.
We did a prospective, double-blind, multicentre, randomised trial to assess treatment with one intravenous dose of MSCs compared with placebo. We recruited ventilated patients with moderate to severe ARDS (ratio of partial pressure of oxygen to fractional inspired oxygen <27 kPa and positive end-expiratory pressure PEEP ≥8 cm H
O) in five university medical centres in the USA. Patients were randomly assigned 2:1 to receive either 10 × 10
/kg predicted bodyweight MSCs or placebo, according to a computer-generated schedule with a variable block design and stratified by site. We excluded patients younger than 18 years, those with trauma or moderate to severe liver disease, and those who had received cancer treatment in the previous 2 years. The primary endpoint was safety and all analyses were done by intention to treat. We also measured biomarkers in plasma. MSC viability was tested in a post-hoc analysis. This trial is registered with ClinicalTrials.gov, number NCT02097641.
From March 24, 2014, to Feb 9, 2017 we screened 1038 patients, of whom 60 were eligible for and received treatment. No patient experienced any of the predefined MSC-related haemodynamic or respiratory adverse events. One patient in the MSC group died within 24 h of MSC infusion, but death was judged to be probably unrelated. 28-day mortality did not differ between the groups (30% in the MSC group vs 15% in the placebo group, odds ratio 2·4, 95% CI 0·5-15·1). At baseline, the MSC group had numerically higher mean scores than the placebo group for Acute Physiology and Chronic Health Evaluation III (APACHE III; 104 SD 31 vs 89 33), minute ventilation (11·1 3·2 vs 9·6 2·4 L/min), and PEEP (12·4 3·7 vs 10·8 2·6 cm H
O). After adjustment for APACHE III score, the hazard ratio for mortality at 28 days was 1·43 (95% CI 0·40-5·12, p=0·58). Viability of MSCs ranged from 36% to 85%.
One dose of intravenous MSCs was safe in patients with moderate to severe ARDS. Larger trials are needed to assess efficacy, and the viability of MSCs must be improved.
National Heart, Lung, and Blood Institute.
The traditional paradigm of hospital surgical ward care consists of episodic bedside visits by providers with periodic perusals of the patient's electronic health record (EHR). Vital signs and ...laboratory results are directly pushed to the EHR but not to providers themselves. Results that require intervention may not be recognized for hours. Remote surveillance programs continuously monitor electronic data and provide automatic alerts that can be routed to multidisciplinary providers. Such programs have not been explored in surgical general care wards.
We performed a quality improvement observational study of otolaryngology and ophthalmology patients on a general care ward from October 2017 to March 2019 during nighttime hours (17:00-07:00). The study was initiated due to the loss of on-site anesthesiology resources that historically helped respond to acute physiologic deterioration events. We implemented a remote surveillance software program to continuously monitor patients for severe vital signs and laboratory abnormalities and automatically alert the ward team and a remote critical care anesthesiology team. The primary end point was the true positive rate, defined as the proportion of alerts that were associated with a downstream action that changed the care of the patient. This was determined using systematic chart review. The secondary end point, as a measure of alarm fatigue, was the average number of alerts per clinician shift.
The software monitored 3926 hospital visits and analyzed 1,560,999 vitals signs and 16,635 laboratories. It generated 151 alerts, averaging 2.6 alerts per week. Of these, 143 (94.7%) were numerically accurate and 8 (5.3%) were inaccurate. Hypoxemia with oxygen saturation <88% was the most common etiology (92, 63%) followed by tachycardia >130 beats per minute (19, 13.3%). Among the accurate alerts, 133 (88.1%) were true positives with an associated clinical action. Actions included a change in management 113 (67.7%), new diagnostic test 26 (15.6%), change in discharge planning 20 (12.0%), and change in level of care to the intensive care unit (ICU) 8 (4.8%). As a measure of alarm fatigue, there were 0.4 alerts per clinician shift.
In a surgical general care ward, a remote surveillance software program that continually and automatically monitors physiologic data streams from the EHR and alerts multidisciplinary providers for severe derangements provided highly actionable alarms at a rate that is unlikely to cause alarm fatigue. Such programs are feasible and could be used to change the paradigm of monitoring.
No effective pharmacotherapy for acute respiratory distress syndrome (ARDS) exists, and mortality remains high. Preclinical studies support the efficacy of mesenchymal stem (stromal) cells (MSCs) in ...the treatment of lung injury. We aimed to test the safety of a single dose of allogeneic bone marrow-derived MSCs in patients with moderate-to-severe ARDS.
The STem cells for ARDS Treatment (START) trial was a multicentre, open-label, dose-escalation, phase 1 clinical trial. Patients were enrolled in the intensive care units at University of California, San Francisco, CA, USA, Stanford University, Stanford, CA, USA, and Massachusetts General Hospital, Boston, MA, USA, between July 8, 2013, and Jan 13, 2014. Patients were included if they had moderate-to-severe ARDS as defined by the acute onset of the need for positive pressure ventilation by an endotracheal or tracheal tube, a PaO2:FiO2 less than 200 mm Hg with at least 8 cm H2O positive end-expiratory airway pressure (PEEP), and bilateral infiltrates consistent with pulmonary oedema on frontal chest radiograph. The first three patients were treated with low dose MSCs (1 million cells/kg predicted bodyweight PBW), the next three patients received intermediate dose MSCs (5 million cells/kg PBW), and the final three patients received high dose MSCs (10 million cells/kg PBW). Primary outcomes included the incidence of prespecified infusion-associated events and serious adverse events. The trial is registered with ClinicalTrials.gov, number NCT01775774.
No prespecified infusion-associated events or treatment-related adverse events were reported in any of the nine patients. Serious adverse events were subsequently noted in three patients during the weeks after the infusion: one patient died on study day 9, one patient died on study day 31, and one patient was discovered to have multiple embolic infarcts of the spleen, kidneys, and brain that were age-indeterminate, but thought to have occurred before the MSC infusion based on MRI results. None of these severe adverse events were thought to be MSC-related.
A single intravenous infusion of allogeneic, bone marrow-derived human MSCs was well tolerated in nine patients with moderate to severe ARDS. Based on this phase 1 experience, we have proceeded to phase 2 testing of MSCs for moderate to severe ARDS with a primary focus on safety and secondary outcomes including respiratory, systemic, and biological endpoints.
The National Heart, Lung, and Blood Institute.
Women are underrepresented in medicine and academic anesthesiology, and especially in leadership positions. We sought to characterize career achievement milestones of female versus male academic ...anesthesiology chairs to understand possible gender-related differences in pathways to leadership.
We conducted a retrospective observational cross-sectional analysis. In November 2019, curricula vitae (CVs) were requested from then-current members of the US Association of Academic Anesthesiology Chairs. Data reflecting accomplishments up to the time of chair appointment were systematically extracted from CVs and analyzed using a mixed methods approach with qualitative content analysis supplemented by descriptive statistics and bivariate statistical testing. Missing data were not imputed.
Seventy-two CVs were received from eligible individuals (response rate 67.3%). The respondent sample was 12.5% women (n = 9), 87.5% men (n = 63), and no transgender or nonbinary people; this is similar to the known gender balance in anesthesiology chairs in the United States. No statistically significant differences in objective markers of academic achievement at the time of chair appointment were evident for female versus male chairs, including time elapsed between the first faculty appointment and assumption of the chair role (median 25 vs 18 years, P = .06), number of publications at the time the chair was assumed (101 vs 69, P = .28), or proportion who had ever held a National Institutes of Health (NIH) grant as principal investigator (44.4% vs 25.4%, 0.25). Four phenotypes of career paths were discernible in the data: the clinician-administrator, the educator, the investigator, and the well-rounded scholar; these did not differ by gender.
Female chairpersons who were members of the Association of Academic Anesthesiology Chairs in the United States demonstrated similar patterns of academic achievement as compared to male chairpersons at the time the position of chair was assumed, suggesting that they were equally qualified for the role as compared to men. Four patterns of career achievements were evident in the chairperson group, suggesting multiple viable pathways to this leadership position.
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