Gender and Pathways to Leadership in Academic Anesthesiology: A Qualitative Content Analysis of US Chairpersons' Curricula Vitae.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

A Remote Surveillance Platform to Monitor General Care Ward Surgical Patients for Acute Physiologic Deterioration.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Controversies in Perioperative Antimicrobial Prophylaxis.

Although clinical guidelines for antibiotic prophylaxis across a wide array of surgical procedures have been proposed by multidisciplinary groups of physicians and pharmacists, clinicians often deviate from recommendations. This is particularly true when recommendations are based on weak data or expert opinion. The goal of this review is to highlight certain common but controversial topics in perioperative prophylaxis and to focus on the data that does exist for the recommendations being made.

Remote Surveillance Technologies: Realizing the Aim of Right Patient, Right Data, Right Time.

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.

Association between Pseudomonas aeruginosa type III secretion, antibiotic resistance, and clinical outcome: a review.

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.

Airway microbiota and bronchial hyperresponsiveness in patients with suboptimally controlled asthma.

BACKGROUND: Improvement in lung function after macrolide antibiotic therapy has been attributed to reduction in bronchial infection by specific bacteria. However, the airway might be populated by a more diverse microbiota, and clinical features of asthma might be associated with characteristics of the airway microbiota present. OBJECTIVE: We sought to determine whether relationships exist between the composition of the airway bacterial microbiota and clinical features of asthma using culture-independent tools capable of detecting the presence and relative abundance of most known bacteria. METHODS: In this pilot study bronchial epithelial brushings were collected from 65 adults with suboptimally controlled asthma participating in a multicenter study of the effects of clarithromycin on asthma control and 10 healthy control subjects. A combination of high-density 16S ribosomal RNA microarray and parallel clone library-sequencing analysis was used to profile the microbiota and examine relationships with clinical measurements. RESULTS: Compared with control subjects, 16S ribosomal RNA amplicon concentrations (a proxy for bacterial burden) and bacterial diversity were significantly higher among asthmatic patients. In multivariate analyses airway microbiota composition and diversity were significantly correlated with bronchial hyperresponsiveness. Specifically, the relative abundance of particular phylotypes, including members of the Comamonadaceae, Sphingomonadaceae, Oxalobacteraceae, and other bacterial families were highly correlated with the degree of bronchial hyperresponsiveness. CONCLUSION: The composition of bronchial airway microbiota is associated with the degree of bronchial hyperresponsiveness among patients with suboptimally controlled asthma. These findings support the need for further functional studies to examine the potential contribution of members of the airway microbiota in asthma pathogenesis.

Wearables alone will not eliminate failure to rescue.

Surveys suggest that anaesthesiologists believe that continuous monitoring with wearables will lead to improved patient outcomes. However, evidence suggests that several critical factors, including timely recognition of physiological problems, the presence of a trained team to respond to the alerts, and that the alerts occur far in advance of the deterioration, are required before overall improvement can occur. Wearables alone will not change patients' outcomes, they must be implemented as part of a system change that takes advantage of the higher frequency observations that continuous monitoring provides.

Therapies against virulence products of Staphylococcus aureus and Pseudomonas aeruginosa.

Methicillin-resistant STAPHYLOCOCCUS AUREUS (MRSA) and PSEUDOMONAS AERUGINOSA are key pathogens in hospitals (particularly intensive care units), in long-term care facilities, and in outpatients with specific comorbidities and risk factors. Both MRSA and P. AERUGINOSA display resistance to a wide array of antibiotics. Further, both bacteria contain a variety of virulence products or systems that make it difficult to treat associated infections. Within the past several years, community-acquired MRSA containing virulence factors [particularly the Panton-Valentine leukocidin (PVL) gene] has emerged globally. Given the limited number of novel antibiotics to treat antibiotic-resistant organisms, there is growing interest in treating bacterial infections by targeting specific virulence products or systems. This article reviews potential therapeutic targets in the virulence systems of these two bacteria that are responsible for a large number of serious infections in critically ill patients.

Polymorphisms in the Pseudomonas aeruginosa type III secretion protein, PcrV - implications for anti-PcrV immunotherapy.

The type III secretion system of Pseudomonas aeruginosa, responsible for acute infection, is composed of over twenty proteins that facilitate cytotoxin injection directly into host cells. Integral to this process is production and secretion of PcrV. Administration of a recently developed, anti-PcrV immunoglobulin, either as a therapeutic or prophylactic has previously demonstrated efficacy against laboratory strains of P. aeruginosa in a murine model. To determine if this therapy is universally applicable to a variety of P. aeruginosa clinical isolates, genetic heterogeneity of pcrV was analyzed among strains collected from three geographically distinct regions; United States, France and Japan. Sequence analysis of PcrV demonstrated limited variation among the clinical isolates examined. Strains were grouped according to the presence of non-synonymous single nucleotide polymorphisms. Representative isolates from each mutant group were examined for the ability of anti-PcrV to bind the protein secreted by these strains. The protective effect of anti-PcrV IgG against each strain was determined using an epithelial cell line cytotoxicity assay. The majority of strains tested demonstrated reduced cytotoxicity in the presence of anti-PcrV IgG. This study provides insights into the natural sequence variability of PcrV and an initial indication of the amino acid residues that appear to be conserved across strains. It also demonstrates the protective effect of anti-PcrV immunotherapy against a multitude of P. aeruginosa strains from diverse global regions with a variety of mutations in PcrV.

Mechanisms of bacterial virulence in pulmonary infections.

PURPOSE OF REVIEW: To consider the relevance to severe human lung infections of recently discovered virulence mechanisms of Staphylococcus aureus and Francisella tularensis. RECENT FINDINGS: S. aureus has long been considered an opportunistic pathogen. However, due to the emergence of community-acquired methicillin-resistant S. aureus (CA-MRSA) strains that can readily infect and kill normal hosts, S. aureus must now be considered a potentially virulent pathogen. The evolution of S. aureus from an organism associated with asymptomatic nasopharyngeal colonization to one associated with community-acquired lethal infections may reflect horizontal acquisition of bacterial genes that enable efficient spread, aggressive host invasion, and effective immune evasion. Alleviating the burden of staphylococcal disease will require better understanding of host susceptibility and of staphylococcal virulence and antibiotic resistance. In contrast to the rapidly evolving staphylococcal virulence strategy, recent genomic analysis of F. tularensis has revealed a small set of bacterial genes associated with the marked virulence of its North American subspecies. This suggests that a relatively stable strategy of immune evasion underlies this pathogen's ability to establish serious life-threatening lung infections from a very small inoculum. SUMMARY: Understanding bacterial pathogenesis will require additional research into both host susceptibility factors and bacterial virulence mechanisms, including horizontal gene transfer. Refinements in the molecular detection of bacteria in the clinical setting, as well as whole genome analysis of both pathogens and patients, are expected to aid in the understanding of bacterial-induced lung injury.

Role of small GTPases and alphavbeta5 integrin in Pseudomonas aeruginosa-induced increase in lung endothelial permeability.

Pseudomonas aeruginosa is an opportunistic pathogen that can cause severe pneumonia associated with airspace flooding with protein-rich edema in critically ill patients. The type III secretion system is a major virulence factor and contributes to dissemination of P. aeruginosa. However, it is still unknown which particular bacterial toxin and which cellular pathways are responsible for the increase in lung endothelial permeability induced by P. aeruginosa. Thus, the first objective of this study was to determine the mechanisms by which this species causes an increase in lung endothelial permeability. The results showed that ExoS and ExoT, two of the four known P. aeruginosa type III cytotoxins, were primarily responsible for bacterium-induced increases in protein permeability across the lung endothelium via an inhibition of Rac1 and an activation of the RhoA signaling pathway. In addition, inhibition of the alphavbeta5 integrin, a central regulator of lung vascular permeability, prevented these P. aeruginosa-mediated increases in albumin flux due to endothelial permeability. Finally, prior activation of the stress protein response or adenoviral gene transfer of the inducible heat shock protein Hsp72 also inhibited the damaging effects of P. aeruginosa on the barrier function of lung endothelium. Taken together, these results demonstrate the critical role of the RhoA/alphavbeta5 integrin pathway in mediating P. aeruginosa-induced lung vascular permeability. In addition, activation of the stress protein response with pharmacologic inhibitors of Hsp90 may protect lungs against P. aeruginosa-induced permeability changes.

An engineered human antibody fab fragment specific for Pseudomonas aeruginosa PcrV antigen has potent antibacterial activity.

Pseudomonas aeruginosa is an opportunistic pathogen that can cause acute lung injury and mortality through the delivery of exotoxins by the type III secretion system (TTSS). PcrV is an important structural protein of the TTSS. An engineered human antibody Fab fragment that binds to the P. aeruginosa PcrV protein with high affinity has been identified and has potent in vitro neutralization activity against the TTSS. The instillation of a single dose of Fab into the lungs of mice provided protection against lethal pulmonary challenge of P. aeruginosa and led to a substantial reduction of viable bacterial counts in the lungs. These results demonstrate that blocking of the TTSS by a Fab lacking antibody Fc-mediated effector functions can be sufficient for the effective clearance of pulmonary P. aeruginosa infection.

Persistent infection with Pseudomonas aeruginosa in ventilator-associated pneumonia.

RATIONALE: Pseudomonas aeruginosa is one of the leading causes of gram-negative ventilator-associated pneumonia (VAP) associated with a mortality rate of 34 to 68%. Recent evidence suggests that P. aeruginosa in patients with VAP may persist in the alveolar space despite adequate antimicrobial therapy. We hypothesized that failure to eradicate P. aeruginosa from the lung is linked to type III secretory system (TTSS) isolates. OBJECTIVES: To determine the mechanism by which infection with P. aeruginosa in patients with VAP may evade the host immune response. METHODS: Thirty-four patients with P. aeruginosa VAP underwent noninvasive bronchoalveolar lavage (BAL) at the onset of VAP and on Day 8 after initiation of antibiotic therapy. Isolated pathogens were analyzed for secretion of type III cytotoxins. Neutrophil apoptosis in BAL fluid was quantified by assessment of nuclear morphology on Giemsa-stained cytocentrifuge preparations. Neutrophil elastase was assessed by immunoenzymatic assay. MEASUREMENTS AND MAIN RESULTS: Twenty-five out of the 34 patients with VAP secreted at least one of type III proteins. There was a significant difference in apoptotic rate of neutrophils at VAP onset between those strains that secreted cytotoxins and those that did not. Neutrophil elastase levels were positively correlated with the rate of apoptosis (r = 0.43, P < 0.01). Despite adequate antimicrobial therapy, 13 out of 25 TTSS(+) isolates were recovered at Day 8 post-VAP, whereas eradication was achieved in all patients who had undetectable levels of type III secretion proteins. CONCLUSIONS: The increased apoptosis in neutrophils by the TTSS(+) isolates may explain the delay in eradication of Pseudomonas strains in patients with VAP. Short-course antimicrobial therapy may not be adequate in clearing the infection with a TTSS secretory phenotype.

The United States critical illness and injury trials group: an introduction.

The US Critical Illness and Injury Trials Group is funded to engage the relevant scientific communities and federal agencies to jointly advocate for clinical research. An inclusive, nationwide network of experts has been created to establish national priorities and pursue a strategic plan in conjunction with professional societies and existing research networks. Investigator-initiated clinical proposals will be presented and discussed at the inaugural National Institutes of Health meeting to promote collaboration and establish working groups to develop projects and core resources. Future US Critical Illness and Injury Trials Group meetings will convene triannually, providing a venue to gauge progress on strategic deliverables, foster development of the clinical projects, discuss education and training in clinical trial design, and address the ethical, legal, and social implications of research in the critically ill or injured patients.