BACKGROUND Current regulations of anaesthesiology training programmes may affect gender equity, female representation and leadership. OBJECTIVE To describe the work regulations of anaesthesiology training programs and working conditions during the early period of child-rearing in European countries. DESIGN Cross-sectional survey. SETTING National Anesthesiologists Societies Committee (NASC) representatives of the European Society of Anesthesiology and Intensive Care. PARTICIPANTS Thirty-eight NASC representatives. MAIN OUTCOME MEASURES Basic specialist training working conditions, gender-related data, return to work after childbirth and workplace policies against discrimination during anaesthesiology specialist training. INTERVENTION(S) A 48-item questionnaire to explore the work patterns and conditions for trainees especially for new parents, professional development opportunities and work discrimination regulations in each representative country was distributed to NASC representatives of 44 European countries. RESULTS We collected the replies of each representative (38 representatives from 44 invited countries' representatives, 86% response rate). The median [IQR] proportion of female trainees was 60% [50 to 68]. There were no reported pay differences between sexes. In eight European countries, pregnant trainees worked fewer hours and were excused from night shifts. Women could not be laid off during pregnancy in all 38 countries (100%). The countries offered a median of 18 weeks of paid (total or partial) maternity leave (range, 13 to 60 weeks). Most countries (89%) accommodate paid paternity leaves. A significant proportion of parental leave was unpaid (n=18, 42%). Twenty-one (55%) countries allowed part-time work after delivery. The UK was the only country with clear recommendations to formally complain after harassment. CONCLUSION European countries have a wide variety of regulations. On paper, numerous countries have various paid maternal, paternal and parental leave; however, it remains to be determined if such leave takes place in practice. The practical consequences of these regulations on female trainees during the child-rearing period need to be explored further.

BackgroundMolecular mechanisms underlying perioperative acute phase reactions in cardiac surgery are largely unknown. We aimed to characterise perioperative alterations of the acute phase plasma proteome in a cohort of adult patients undergoing on-pump cardiac surgery using high-throughput mass spectrometry and to identify candidate proteins potentially relevant to postoperative clinical outcome through a novel, multi-step approach.MethodsThis study is an analysis of the Bern Perioperative Biobank, a prospective cohort of adults who underwent cardiac surgery with the use of cardiopulmonary bypass (CPB) at Bern University Hospital between January and December 2019. Blood samples were taken before induction of anaesthesia and on postoperative day one. Proteomic analyses were performed by mass spectrometry. Through a multi-step, exploratory approach, hit-proteins were first identified according to their perioperative prevalence and dynamics. The set of hit-proteins were associated with predefined clinical outcome measures (all-cause one-year mortality, length of hospital stay, postoperative myocardial infarction and stroke until hospital discharge).Results192 patients [75.5% male, median age 67.0 (IQR 60.0–73.0)] undergoing cardiac surgery with the use of CPB were included in this analysis. In total, we identified and quantified 402 proteins across all samples, whereof 30/402 (7%) proteins were identified as hit-proteins. Three hit-proteins—LDHB, VCAM1 and IGFBP2—demonstrated the strongest associations with clinical outcomes. After adjustment both for age, sex, BMI and for multiple comparisons, the scaled preoperative levels of IGFBP2 were associated with 1-year all-cause mortality (OR 10.63; 95% CI: 2.93–64.00; p = 0.046). Additionally, scaled preoperative levels of LDHB (OR 5.58; 95% CI: 2.58–8.57; p = 0.009) and VCAM1 (OR 2.32; 95% CI: 0.88–3.77; p = 0.05) were found to be associated with length of hospital stay.ConclusionsWe identified a subset of promising candidate plasma proteins relevant to outcome after on-pump cardiac surgery. IGFBP2 showed a strong association with clinical outcome measures and a significant association of preoperative levels with 1-year all-cause mortality. Other proteins strongly associated with outcome were LDHB and VCAM1, reflecting the dynamics in the acute phase response, inflammation and myocardial injury. We recommend further investigation of these proteins as potential outcome markers after cardiac surgery. Clinical Trial RegistrationClinicalTrials.gov; NCT04767685, data are available via ProteomeXchange with identifier PXD046496.

BACKGROUND: Postoperative complications in surgery are a significant burden, not only for the patients but also economically. While several predicting factors have already been identified, it is still not well known if increased levels of inflammatory markers in the immediate perioperative phase correlate with a higher incidence of postoperative complications. This study aimed to evaluate which patient characteristics and intraoperative parameters correlate with increased plasma values of monocyte chemoattractant protein 1 (MCP-1) and interleukin 6 (IL-6) of thoracic surgery patients. A second goal was to explore whether MCP-1 and IL-6 are associated with the incidence of postoperative complications. We hypothesized that there is a positive association between inflammatory markers and the occurrence of complications within 6 months after surgery. METHODS: This is a substudy of a recent randomized controlled trial, which defined the effect of desflurane versus propofol anesthesia on morbidity and mortality in patients undergoing thoracic surgery. MCP-1 and IL-6 were determined in plasma obtained before and 30 minutes after 1-lung ventilation, 6 hours after surgery, and on postoperative days 1 and 2. Complications were recorded for 6 months. Mixed linear models were used to examine factors associated with MCP-1 and IL-6 levels. Logistic regression models and receiver operating characteristic curves were used to determine the association between MCP-1 and IL-6 and postoperative complications. RESULTS: In the original study, 460 patients were included, MCP-1 and IL-6 levels were determined in 428 patients. MCP-1 was positively associated with the duration of surgery ( P = .016), whereas IL-6 levels increased with both the length ( P < .001) and invasiveness of lung surgery (thoracoscopic wedge resection or lobectomy versus open lobectomy, P = .005; thoracoscopic wedge resection or lobectomy versus pneumonectomy, P = .021). In an exploratory approach, elevated IL-6 plasma peaks were associated with the occurrence of severe complications defined as Clavien-Dindo score grade ≥IVa during the postoperative phase up to 6 months after thoracic surgery ( P = .006). CONCLUSIONS: In summary, this substudy reveals factors, which correlate with high MCP-1 and IL-6 values. Moreover, higher IL-6 seems to be associated with postoperative severe complications. Perioperative IL-6 monitoring might be helpful for risk estimation in the perioperative setting of patients after lung surgery.

BACKGROUND: Health care worker (HCW) safety is of pivotal importance during a pandemic such as coronavirus disease 2019 (COVID-19), and employee health and well-being ensure functionality of health care institutions. This is particularly true for an intensive care unit (ICU), where highly specialized staff cannot be readily replaced. In the light of lacking evidence for optimal staffing models in a pandemic, we hypothesized that staff shortage can be reduced when staff scheduling takes the epidemiology of a disease into account. METHODS: Various staffing models were constructed, and comprehensive statistical modeling was performed. A typical routine staffing model was defined that assumed full-time employment (40 h/wk) in a 40-bed ICU with a 2:1 patient-to-staff ratio. A pandemic model assumed that staff worked 12-hour shifts for 7 days every other week. Potential in-hospital staff infections were simulated for a total period of 120 days, with a probability of 10%, 25%, and 40% being infected per week when at work. Simulations included the probability of infection at work for a given week, of fatality after infection, and the quarantine time, if infected. RESULTS: Pandemic-adjusted staffing significantly reduced workforce shortage, and the effect progressively increased as the probability of infection increased. Maximum effects were observed at week 4 for each infection probability with a 17%, 32%, and 38% staffing reduction for an infection probability of 0.10, 0.25, and 0.40, respectively. CONCLUSIONS: Staffing along epidemiologic considerations may reduce HCW shortage by leveling the nadir of affected workforce. Although this requires considerable efforts and commitment of staff, it may be essential in an effort to best maintain staff health and operational functionality of health care facilities and systems.

Venoarterial extracorporeal membrane oxygenation (vaECMO) is a well-established treatment option for severe cardiogenic shock of various etiologies. Although trials have explored weaning strategies, a brief and conclusive overview is lacking. We present the different aspects of weaning and provide an evidence- and experienced-based guide for clinicians managing patients under vaECMO in the preweaning, weaning, and postweaning phases.

BACKGROUND:The cellular immune system is of pivotal importance with regard to the response to severe infections. Monocytes/macrophages are considered key immune cells in infections and downregulation of the surface expression of monocytic human leukocyte antigen-DR (mHLA-DR) within the major histocompatibility complex class II reflects a state of immunosuppression, also referred to as injury-associated immunosuppression. As the role of immunosuppression in coronavirus disease 2019 (COVID-19) is currently unclear, we seek to explore the level of mHLA-DR expression in COVID-19 patients. METHODS:In a preliminary prospective monocentric observational study, 16 COVID-19-positive patients (75% male, median age: 68 [interquartile range 59-75]) requiring hospitalization were included. The median Acute Physiology and Chronic Health Evaluation-II (APACHE-II) score in 9 intensive care unit (ICU) patients with acute respiratory failure was 30 (interquartile range 25-32). Standardized quantitative assessment of HLA-DR on monocytes (cluster of differentiation 14+ cells) was performed using calibrated flow cytometry at baseline (ICU/hospital admission) and at days 3 and 5 after ICU admission. Baseline data were compared to hospitalized noncritically ill COVID-19 patients. RESULTS:While normal mHLA-DR expression was observed in all hospitalized noncritically ill patients (n = 7), 89% (8 of 9) critically ill patients with COVID-19-induced acute respiratory failure showed signs of downregulation of mHLA-DR at ICU admission. mHLA-DR expression at admission was significantly lower in critically ill patients (median, [quartiles]: 9280 antibodies/cell [6114, 16,567]) as compared to the noncritically ill patients (30,900 antibodies/cell [26,777, 52,251]), with a median difference of 21,508 antibodies/cell (95% confidence interval [CI], 14,118-42,971), P = .002. Reduced mHLA-DR expression was observed to persist until day 5 after ICU admission. CONCLUSIONS:When compared to noncritically ill hospitalized COVID-19 patients, ICU patients with severe COVID-19 disease showed reduced mHLA-DR expression on circulating CD14+ monocytes at ICU admission, indicating a dysfunctional immune response. This immunosuppressive (monocytic) phenotype remained unchanged over the ensuing days after ICU admission. Strategies aiming for immunomodulation in this population of critically ill patients should be guided by an immune-monitoring program in an effort to determine who might benefit best from a given immunological intervention.

GLOSSARY ASA = American Society of Anesthesiologists; IARS = International Anesthesia Research Society There will be no female leaders—there will just be leaders. —Sheryl Sandberg, Chief Operating Officer, Facebook, 20131 It has been a quarter of a century since the US Glass Ceiling Commission published the report Glass Ceiling Commission – A Solid Investment: Making Full Use of the Nation's Human Capital in 1995.2 But barriers to the inclusion and advancement of women in business—and by extension in medicine—still stand around the world. The concept of a glass ceiling—defined by Merriam-Webster as "an intangible barrier within a hierarchy that prevents women or minorities from obtaining upper-level positions"—is well known. The glass ceiling is a barrier women face across a broad range of professions, not just medicine. What steps can we take to enact change in anesthesia and acute care medicine? Here we bring together articles from business and human resource sciences, recommendations for involving women in leadership and gender diversity programs, and the experience and knowledge of women in leadership positions, in an attempt to move toward Sheryl Sandberg's vision of a world in which "there will be no female leaders—there will just be leaders."1 THE STATUS OF WOMEN US-derived data show that women remain underrepresented in leadership roles in most aspects of anesthesiology and acute care, from positions as faculty members and chairpersons in medical schools to service on editorial boards of anesthesiology journals to presidencies of professional societies.3 Yet, Bissing et al3 recently found "some indications that women may be on the path to leadership parity." Recognizing the importance of scientific publications for an academic career, Miller et al4 recently showed an increase of 10% and 9%, respectively, in first and senior authorships by women in 2 major anesthesia journals between 2002 and 2017. Caroline Palmer, Isabella Herb, Virginia Apgar, Mary Botsford, Bette Stephenson, Judith Donegan, and Gertie Marx are just a few of the pioneering women who have contributed their talents and passion to the field of anesthesiology. Palmer, who advocated recognition of anesthesiology as a medical specialty in the early 1900s, was the first chief of anesthesia at Stanford University.5 Her choice of specialty was possibly influenced by the prevailing attitude that anesthesiology was especially suited for women (19% of the members of the American Association of Anesthetists were women in 1916, but only 3.6% of physicians nationally).6 In 1923, Dr Palmer published recommendations for organizing an anesthesiology department that were far ahead of their time and nearly indistinguishable from those currently practiced in university hospitals.7 Although these women were ultimately recognized for their many contributions to the field, their academic careers did not always develop universally upward. Limiting opportunities for women limits contributions. Importantly, in medicine, a diverse workforce may improve outcomes.8 Indeed, some evidence suggests that patients treated by women specializing in internal medicine may have lower mortality rates than patients being treated by men in that specialty.8 More than a decade ago, Weeks et al9 showed that female anesthesiologists' mean incomes were 20% lower than that of males in the United States9 In spite of the significant increase in the number of female specialists between 2007 and 2013, age-corrected and practice-type-corrected disparities in compensation remain, for reasons not understood.10 Gender is associated with income disparity globally and in anesthesiology.9,10 Unfortunately, original data and non–US-derived publications are sparse; however, data from India show that only 42% of highly educated women currently earn as much as or more than their spouses.11 MALE-DOMINATED NETWORKS AND A LACK OF ROLE MODELS Opportunities for women can be limited by society and culture. This was particularly true in the past. Historically, professional networking and relationship building often took place at informal get-togethers, sometimes in locations (such as "men-only bars" or country clubs) that were off-limits to women.12 And in many Western countries, after-work gatherings and retreats were held in masculine environments, intentionally or not, where some women might have felt less comfortable. These meetings often occurred in the evenings and on weekends, when women had competing family obligations.12 Crucial discussions were sometimes held in seemingly casual moments.12 Although this reference is >25 years old, such dimensions might still be a reality in many professional settings today.12,13 Yet, opportunities may also be limited in systems which are led by women. Although women have increased their presence in some male-dominated professions, such as accounting and journalism, they continue to have difficulty overcoming "macho" stereotypes in professions such as surgery, a traditionally masculine occupation.13 Interestingly, Peters et al13 found that there are also male surgical trainees who feel they are "not man enough" to fit in. In their article "Women Rising: the Unseen Barriers," Ibarra et al14 identified "second-generation gender bias" as the main cause of women's underrepresentation in leadership. This bias stems from a paucity of women as role models to identify with in business as well as in medicine, and a definition of leadership that includes typically masculine traits.14 The lack of women in top positions "reinforces entrenched beliefs" and "prompts and supports men's bids for leadership," according to the authors.14 Because there are few women to serve as role models, up-and-coming female leaders may get the impression that senior women are not credible sources of advice and support.14 Safe settings need to be created for women through support groups, coaching, and a women's leadership program, say the authors. CHARACTER TRAITS A milestone article by Fels15 addressed the question: "Do women lack ambition?" Her research showed that women associate the word "ambition" with egoism, self-centeredness, and exploitation of others, whereas men see ambition as both a desirable trait and necessary for success. Fels15 importantly notes that both women and men have great ambitions in their youth. However, over time, women tend not to receive the same recognition for their achievements as men do, leading to attrition of their ambition.15 Unlike men, women often shun recognition and deflect attention from themselves. Fels15 advises women to organize politically, to blow their own horns, and not to expect professional success to fall into place. It is never too late to benefit from powerful mentors, opportunities to learn new skills, promotion, collegial support, and institutional recognition, she says. While women are competitive with other women, or in roles that complement those of men, they often avoid direct competition with men. Culturally, Fels15 says, femininity is linked with social relationships and giving, traits not associated with masculinity. Are women more emotionally intelligent than men? "Yes and no," says Daniel Goleman, an expert in the field of emotional intelligence. He notes that women tend to attune themselves to others' emotions, whereas men tend to solve the emotions' underlying problem (http://www.danielgoleman.info/are-women-more-emotionally-intelligent-than-men). The latter might (wrongly) be perceived as "more professional," Goleman says, although both behavioral patterns obviously have their advantages in acute care medicine. FAMILY OBLIGATIONS Women are often expected to first satisfy the needs of their family before pursuing their own careers and ambitions.14–16 Whether it's to raise children or to care for aging parents, women modify their career paths more often than men.16 These interruptions can be difficult to recover from. Hewlett and Luce16 examined whether women are "pushed off" or "pulled off" career paths, and found that most women aspire to return, but too often, their options are limited. Thus employers need to enable women to easily get back on the "on-ramp."16 As more industries accept and encourage men to take paternity leave, and society becomes accustomed to men being equal partners in raising children, women will perhaps feel better able to share the responsibility for meeting the social needs of the family. MENTORING Support—in the form of role models, mentoring, and networking—is crucial for women who want to become leaders. Ibarra et al14 highlighted the importance of creating a safe setting, such as a coaching relationship within a women's leadership program, or a peer support group, to enable women to compare notes, identify common experiences, and support one another's learning. Mentoring can have a positive impact on personal development, career choice, and research productivity, according to Miller et al,4 who found that women represented a higher percentage of first authors on papers with women as senior authors. Rose et al,17 who wrote on trends in gender distribution, emphasized that women must be supported by strong mentors and actively prepared to assume leadership roles in anesthesiology organizations, with particular emphasis placed on involving women faculty as personal, clinical, and research advisors and as mentors. While many women feel more comfortable with female advisors, there is strong evidence that there are distinct benefits from men mentoring women.18 These benefits accrue for the mentor, the mentee, and the group in general. These male supporters possess common ideals, including using position to advocate for gender equality, believing gender inclusiveness is part of effective talent management, providing gender-aware mentoring and coaching, and practicing other-focused leadership, not self-focused leadership.18 Unfortunately, these male allies may be rare.18 Bissing et al3 recently concluded that "with more early- and midcareer women in the field, there is the opportunity not only for these women to climb the academic ranks into the highest leadership positions in the field but also to advocate for other women more junior than themselves, allowing for an infrastructure of women mentoring." Margaret Wood, who in 1955 became the first female physician to chair a clinical department at Columbia University, stated that successful and experienced female leaders play an important role as advisors of junior faculty and residents, and can "pull women up" through one-on-one mentorship and coaching.19 But she cautioned: "It would be a tragedy for women leaders of the future if they felt they had to receive their education and mentoring exclusively from women rather than men."19 NETWORKING A network can help advance a candidate to the leadership level. The first anesthesia society, specifically for women, Women in Anesthesiology, was created to help women in anesthesiology "advance in their careers while addressing the specific challenges women physicians may face" (https://www.womeninanesthesiology.org/). Yang et al20 recently analyzed the gender composition of graduate students' social networks and found that certain aspects of the networks strongly predicted placement into leadership positions after graduation. Whereas for male students being at the center of a large network was key, regardless of the group's gender make-up, high-placing female students also had an inner circle of 2 or 3 other well-connected women who communicated intensely with each other and had a large number of nonoverlapping contacts.20 Contact with both men and women appears to be crucial for both genders who strive to be leaders. Interpreting his group's research for the Harvard Business Review, coauthor Uzzi21 suggested that women can benefit from a strategic approach to networking that includes (1) seeking quality over quantity in one's overall network, (2) identifying and connecting to people who are connected to multiple networks, and (3) being wary of an isolated inner circle, which can feel socially secure but fails to generate key insights and opportunities. In 2017, Toledo et al22 studied diversity (or rather, the lack thereof) in the leadership of the American Society of Anesthesiologists (ASA). Based on the results of a survey, they found that women are underrepresented in the Society in terms of leadership roles, in comparison with their proportion of the medical workforce and of the US population overall.22 In an editorial commenting on the study, Leslie et al23 proposed 10 "rules" for increasing the participation of women in anesthesiology leadership: (1) collect the data, (2) develop a policy, (3) make the policy visible, (4) establish an informed and balanced recruitment group, (5) report the data, (6) build and use databases, (7) respond to resistance, (8) support women and minority office bearers, (9) be family-friendly, and (10) take the pledge. The authors called on the ASA to "model gender diversity rather than just reflect it." EMPLOYER ATTITUDES In October 2018, the ASA approved a Statement on Personal Leave (https://www.asahq.org/standards-and-guidelines/statement-on-personal-leave) calling on employers to "promote wellness and foster a culture that is conducive to physician well-being, which includes allowing leave for personal and mental health reasons"—for men as well as for women. Specifically mentioned were serious personal illness, the birth or adoption of a child, the care of a sick family member, and mental health emergencies, including burnout. It is also important for acute care disciplines such as anesthesiology to mandate a minimum level of training. It will be the mentors' and superiors' responsibility to ensure that training is not inferior due to part-time work (which, unlike in the United States, is possible, eg, in most European settings). Employers must do their share to support women interested in leadership roles. Fels15 called on institutions to acknowledge and address the biological and cultural barriers that women face, and to enable women to work toward mastering skills and feeling comfortable attracting recognition. Hewlett and Luce16 recommend that organizations focus on creating flexible work schedules, such as variable workdays and reduced hours per day, and provide career models that are as individual as possible. Because we cannot always manage the factors that pull women away from their jobs, say the authors, we have to avoid the factors that push them away. Astute leaders in anesthesiology and medicine understand that there are both biological and cultural barriers for women, and thus indirectly, for men too. Anesthesiology offers excellent possibilities to offer flexible work schedules and individual career models. Rose et al17 highlighted the importance of educating the workforce about the problems deriving from gender inequality. LARGE-SCALE APPROACHES TO SYSTEMIC CHANGE Not only employers and societies but entire countries can effect change. In 2010, US President Barack Obama nominated a woman—Elena Kagan, the first female dean of Harvard Law School—for a position on the Supreme Court, the country's highest judicial body. Her confirmation increased the proportion of women serving on the court to 3 of 9 members, or one-third. An online article describing the appointment, titled "What the U.S. can learn from Europe about gender equality in the workplace" (https://hbr.org/2010/05/wake-up-obama-gender-equality), touted significant efforts proposed by the British, Dutch, French, German, and Norwegian governments to reach gender equality, and the resulting benefits for the economy: thinking in silos is reduced, productivity goes up, and returns on investments are higher in companies striving for gender equality. In Europe, an innovative project called "Medicine Goes Female" was created to address the growing need for additional health care personnel in European countries due to changing demographics, and the expectation that women will soon outnumber men as physicians in Europe.24 "Medicine Goes Female" will address the needs of women in medicine by facilitating the implementation of Gender Equality Plans in 8 university hospitals in 7 countries: Germany, Norway, Lithuania, Poland, the Netherlands, the Czech Republic, and Italy.24 Web-based surveys will be used to identify "cultural, country-specific, and interdisciplinary factors conducive to women's academic success," and gender equality in academic medicine will be discussed in workshops and via an online platform. Findings will be used to prepare case studies for academic teaching on leadership and management. A European consulting service is envisioned, with support and consulting services for hospitals. The initial project will focus on gender equality in anesthesiology and surgery. In the United States, anesthesiology and acute care medicine are already facing significant staffing challenges related to the aging of society and increasing demand for health care. US data show too few women in the anesthesia pipeline.3 Although medical school classes consist of >50% women, only 36% choose anesthesiology as a specialty.3 Strategies to hire and specifically to retain talented employees of both sexes are of utmost importance. At the 2019 annual meeting of the International Anesthesia Research Society (IARS) in Montreal, Canada, a session entitled "Encouraging the Next Generation of Women: Growing Junior Faculty as Leaders" was presented (Table). In many ways, the session mirrored the problem. The 5 women who presented—ranging from Millennials to Baby Boomers—had been educated at top schools and hold positions of responsibility. Their presentations—reflecting their varied viewpoints and experiences—covered a range of issues, from leveraging generational differences to leadership styles to saying no strategically. However, there were only a handful of men in the audience, when in fact, this session was of utmost importance for everyone (personal observation of the authors at the 2019 annual meeting of IARS).Table.: Suggestions for the Next Generation of Leaders, Shared by the Speakers at the 2019 IARS Annual MeetingaReaching gender parity will require today's leaders to identify and sponsor the women leaders of tomorrow. At the IARS Congress, Colleen Koch, chief of anesthesiology at Johns Hopkins University School of Medicine, brought that message home. "For women, you've got to have mentorship and you've got to have training and you've got to have experiences," she said. The leader in charge of a search committee has to demand a diverse list of candidates. "Go find that talented woman who can do the job!" OPENING THE SKYLIGHTS WITH A MULTIDIMENSIONAL PERSPECTIVE AND A COMMITTED PLAN OF ACTION Achieving gender parity in acute care medicine should not focus on women as "victims" of an unjust system. Rather, the goal should be to level the playing field for the benefit of everyone. Both women and men must recognize that change is not an event but a process that needs to be planned strategically in advance.25 It requires time and has to follow specific steps. Shortcuts are associated with failures.26 The Figure displays the complexity of achieving gender parity in acute care medicine. Even though it is tempting to suggest a "one size fits all" approach to achieve this vision, cultural differences among individuals, institutions, and systems must be considered individually.Figure.: While there is evidence from business and human resource sciences as well from acute care medicine, evidence remains in respective silos and must be integrated into a multidimensional perspective to achieve gender parity in acute care medicine. Replacing the glass ceiling with skylights that open to equal opportunities for all will only be successful if the plan of action addresses societal change, personals traits and family cultures, interactions in individuals' communities and networks, and professional environments. All of these highly linked entities must redefine their missions toward the vision of "achieving gender parity." Cultural and societal forces will remain the key foundations for this mission.Efforts to attain overall equality can only be successful if all players understand and acknowledge biological and cultural differences and barriers, fight "second-generation bias," organize support networks, allow flexible work schedules and career models, show empathy, foster skilled gender-blind role models, and redesign health care organizations. Now is the time to start acting. Our goal should be to include leaders with many different character traits and to overcome the subtle perception that "masculine character traits" are necessary in leaders. If we want to achieve gender parity in acute care medicine, we must broaden our horizons and integrate evidence from business and human resource sciences as well as from acute care medicine into a multidimensional perspective. We call on our colleagues to redefine their personal missions and on the acute care community to implement multidimensional efforts that contribute toward a shared vision. With a concerted effort, the glass ceiling can be replaced with skylights that open to equal opportunities for all. This starts with committed personal perspectives, interactions in individuals' communities and networks, and professional environments that nurture cultural change at every level. This approach will enable lasting and meaningful progress toward a universal standard that will work to the benefit of everyone. DISCLOSURES Name: Nadja Fisler, MD. Contribution: This author helped write the article. Conflicts of Interest: None. Name: Bobbie Jean Sweitzer, MD, FACP. Contribution: This author helped write the article. Conflicts of Interest: B. J. Sweitzer is an Anesthesia & Analgesia editorial board member. Name: Jeannie Wurz, BA. Contribution: This author helped write the article. Conflicts of Interest: None. Name: Amanda M. Kleiman, MD. Contribution: This author helped write the article. Conflicts of Interest: A. M. Kleiman is an Anesthesia & Analgesia editorial board member. Name: Frank Stueber, MD. Contribution: This author helped write the article. Conflicts of Interest: None. Name: Markus M. Luedi, MD, MBA. Contribution: This author helped write the article. Conflicts of Interest: M. M. Luedi is an Anesthesia & Analgesia editorial board member. This manuscript was handled by: Nancy Borkowski, DBA, CPA, FACHE, FHFMA.

Background Microembolism is a frequent pathological event during extracorporeal renal replacement therapy (RRT). Some previous data indicate that microemboli are generated in patients who are undergoing RRT and that these may contribute to increased cerebrovascular and neurocognitive morbidity in patients with end-stage renal disease. The current trial aims to quantify the microembolic load and respective qualitative composition that effectively reaches the intracerebral circulation in critically ill patients treated with different RRT modalities for acute kidney injury (AKI). Methods/design The COMET-AKI trial is a prospective, randomized controlled clinical trial with a 2-day clinical assessment period and follow-up visits at 6 and 12 months. Consecutive critically ill patients with AKI on continuous renal replacement therapy (CRRT) scheduled for a switch to intermittent renal replacement therapy (IRRT) will be randomized to either switch to IRRT within the next 24 h or continued CRRT for an additional 24 h. Cerebral microembolic load will be determined at baseline, i.e., before switch (on CRRT for both groups) and on IRRT versus CRRT, whichever group they were randomized to. The primary endpoint is defined as the difference in mean total cerebral microemboli count during the measurement period on CRRT versus IRRT following randomization. Microemboli will be assessed within the RRT circuit by a 1.5-MHz ultrasound detector attached to the venous RRT tubing and cerebral microemboli will be measured in the middle cerebral artery using a 1.6-MHz robotic transcranial Doppler system with automatic classification of Doppler signals as solid or gaseous. In addition to Doppler measurements, patients will be examined by magnetic resonance imaging and neurocognitive tests to gain better understanding into the potential morphological and clinical consequences of embolization. Discussion The results of COMET-AKI may help to gain a better insight into RRT modality-associated differences regarding microbubble generation and the cerebral microembolic burden endured by RRT recipients. Furthermore, identification of covariates of microbubble formation and distribution may help to encourage the evolution of next-generation RRT circuits including machinery and/or filters. Trial registration ClinicalTrials.gov, ID: NCT02621749 . Registered on 3 December 2015.

Objectives: While several factors have been shown to influence operating room (OR) turnaround times, few comparisons of planned and actual OR turnaround times have been performed. This study aimed to compare planned and actual OR turnaround times at a large rural hospital in Northern Germany. Methods: This retrospective study examined the OR turnaround data of 875 elective surgery cases scheduled at the Marienhospital, Vechta, Germany, between July and October 2014. The frequency distributions of planned and actual OR turnaround times were compared and correlations between turnaround times and various factors were established, including the time of day of the procedure, patient age and the planned duration of the surgery. Results: There was a significant difference between mean planned and actual OR turnaround times (0.32 versus 0.64 hours; P <0.001). In addition, significant correlations were noted between actual OR turnaround times and the time of day of the surgery, patient age, actual duration of the procedure and staffing changes affecting the surgeon or the medical specialty of the surgery (P <0.001 each). The quotient of actual/planned OR turnaround times ranged from 1.733–3.000. Conclusion: Significant discrepancies between planned and actual OR turnaround times were noted during the study period. Such findings may be potentially used in future studies to establish a tool to improve OR planning, measure OR management performance and enable benchmarking.

OBJECTIVEDexamethasone, a known regulator of mesenchymal programming in glioblastoma (GBM), is routinely used to manage edema in GBM patients. Dexamethasone also activates the expression of genes, such as CEBPB, in GBM stem cells (GSCs). However, the drug’s impact on invasion, proliferation, and angiogenesis in GBM remains unclear. To determine whether dexamethasone induces invasion, proliferation, and angiogenesis in GBM, the authors investigated the drug’s impact in vitro, in vivo, and in clinical information derived from The Cancer Genome Atlas (TCGA) cohort.METHODSExpression profiles of patients from the TCGA cohort with mesenchymal GBM (n = 155) were compared with patients with proneural GBM by comparative marker selection. To obtain robust data, GSCs with IDH1 wild-type (GSC3) and with IDH1 mutant (GSC6) status were exposed to dexamethasone in vitro and in vivo and analyzed for invasion (Boyden chamber, human-specific nucleolin), proliferation (Ki-67), and angiogenesis (CD31). Ex vivo tumor cells from dexamethasone-treated and control mice were isolated by fluorescence activated cell sorting and profiled using Affymetrix chips for mRNA (HTA 2.0) and microRNAs (miRNA 4.0). A pathway analysis was performed to identify a dexamethasone-regulated gene signature, and its relationship with overall survival (OS) was assessed using Kaplan-Meier analysis in the entire GBM TCGA cohort (n = 520).RESULTSThe mesenchymal subgroup, when compared with the proneural subgroup, had significant upregulation of a dexamethasone-regulated gene network, as well as canonical pathways of proliferation, invasion, and angiogenesis. Dexamethasone-treated GSC3 demonstrated a significant increase in invasion, both in vitro and in vivo, whereas GSC6 demonstrated a modest increase. Furthermore, dexamethasone treatment of both GSC3 and GSC6 lines resulted in significantly elevated cell proliferation and angiogenesis in vivo. Patients with mesenchymal GBM had significant upregulation of dexamethasone-regulated pathways when compared with patients with proneural GBM. A prognostic (p = 0.0007) 33-gene signature was derived from the ex vivo expression profile analyses and used to dichotomize the entire TCGA cohort by high (median OS 12.65 months) or low (median OS 14.91 months) dexamethasone signature.CONCLUSIONSThe authors present evidence that furthers the understanding of the complex effects of dexamethasone on biological characteristics of GBM. The results suggest that the drug increases invasion, proliferation, and angiogenesis in human GSC-derived orthotopic tumors, potentially worsening GBM patients’ prognoses. The authors believe that careful investigation is needed to determine how to minimize these deleterious dexamethasone-associated side effects in GBM.

OBJECTIVE:Toll-like receptor 4 (Tlr-4) mediates many biological effects of lipopolysaccharide (LPS), which has antitumoral effects on glioblastoma both in vivo and in vitro. However, the precise role of Tlr-4 in these antitumoral effects remains unknown.METHODS:The role of Tlr-4 in the antitumoral effect of LPS on glioblastomas was assessed in wild-type BALB/c mice and in Tlr-4 knockout (KO) BALB/c mice. Mice were implanted with DBT glioblastoma cells intracranially or subcutaneously, were treated with intratumoral LPS, and were assessed by histopathological examination for degrees of tumor progression and inflammation. Flow cytometry and Western blotting with antibodies to the Tlr-4 receptor and flow cytometry to the related CD14 moiety were performed to quantitate the expression levels of these two receptors by glioblastoma cells.RESULTS:For subcutaneous tumors, LPS caused near complete tumor elimination in wild-type mice, but only a 50% reduction in Tlr-4 KO mice. For mice implanted with intracranial glioblastomas, LPS increased survival times modestly in wild-type mice, but showed no benefit in the Tlr-4 KO mice. There were no histological differences among wild-type and Tlr-4 KO mice, except for tumor size. In both models, an early neutrophilic and later macrophage-rich inflammatory infiltrate were seen after LPS administration. Quantitative flow cytometry and Western blotting showed no Tlr-4 receptor or CD14 expression in murine and human glioblastoma cells in vitro, and Western blotting suggested that Tlr-4 effects are mediated by nontumoral elements such as microglia and inflammatory cells.CONCLUSION:LPS-induced antitumoral effects on glioblastoma multiforme are mediated, in part, by the Tlr-4 receptor. Further understanding of this process may lead to novel treatment strategies for this uniformly fatal disease.

Zinn, Pascal O MD, PhD; Luedi, Markus M MD; Singh, Sanjay K PhD; Mosley, Jennifer; Hassan, Islam; Hatami, Masumeh; Gumin, Joy BS; Andereggen, Lukas MD; Sulman, Erik P MD, PhD; Lang, Frederick F MD; Stueber, Frank; Fuller, Gregory N MD, PhD; Colen, Rivka R MD

"IQ and technical skills are important, but emotional intelligence is the sine qua non of leadership." Daniel Goleman The attractiveness of medical careers remains evident worldwide with ever increasing applicant pools. The world's population is aging, medical interventions continue to expand, and purchasing power worldwide continues to drive the demand for physician services. Because there are far fewer positions than applicants for medical education, selection pressure is significant. Test scores, class ranking, advanced degrees, numbers of publications, rotations in the field of interest, and active scientific engagement have all been used as proxy measures of aptitude.1 However, it appears that our resident interview process may not be as useful as perceived and may not predict subsequent performance as either a trainee or as an attending physician.2–4 In addition, 20% of physicians will have a psychological health issue during their career, reports of burnout among anesthesiologists are becoming more frequent,5–8 and the lack of effective tools for managing stress and burnout in the medical profession is increasingly recognized as a problem.9 Thus, it is timely to ask how we might improve resident selection in the specialty, and how we might support fully trained anesthesiologists throughout their careers. A decade ago, a milestone study in management sciences showed that "Emotional Intelligence" (EI)—defined by the psychological dimensions of self-awareness, self-regulation, motivation, empathy, and social skills—affects the performance of leaders. EI has been described as helping to "provide the fundamental groundwork" to ensure that operating room leadership promotes high-quality and safe patient care.10 Reliability of EI measurements in the medical professions has been questioned11; nonetheless, it is apparent that certain aspects of EI have predictive value in the performance of anesthesiology residents,12 and some anesthesiology training programs have begun incorporating the aspects of personality in their resident selection processes.4 Although it remains unclear whether EI is a learnable function, an inherent trait, or a combination of the two,11 it is possible that the negative consequences of a lack of EI may be mitigated through education, mentorship, and collegial support. Several aspects of EI correspond to competencies that medical training seeks to deliver.13 Empathy, organizational awareness, the ability to influence, provide role modeling, and motivate others—all components or consequences of EI—are among the necessary attributes of successful team leaders.14 As leaders in perioperative medicine, anesthesiologists must also possess reliable strategies for self-management to cope with daily work; this is especially important in large hospitals with multiple surgical departments where situational adaptation and coordination between an operating room's stakeholders can pose challenges15 for aligning patient safety, surgeon access to scheduled operating time, and operating room efficiency.16 "Adaptive coordination," a component of EI defined as "the situational management of coordination requirements,"17 is known to be a key characteristic of high performing teams,18 especially in more complex settings such as among a multicultural and multidisciplinary workforce.19 An organizational culture that supports adaptive coordination directed toward group orientation and reduced hierarchy is associated with an increased safety climate.20 Given that possession of EI is an important characteristic of perioperative team leadership relevant to providing high-quality and safe patient care in anesthesiology and acute care medicine, it might be prudent to assess the relevant personality characteristics of resident applicants in addition to the traditional proxy measurements of aptitude noted above. Reliability, honesty, ability to function under stress, punctuality, and discipline have been described as desirable personality traits (ie, a person's fixed patterns of behaviors revealed in different situations, influenced by the person's EI, thus affecting their adaptive coordination) in anesthesia residents.21 In a small, single-center cohort, Merlo et al found that personality traits "may be associated with success" in anesthesiology residency programs.22 In this regard, it should not be surprising that, although the personality type of anesthesiology residents was not associated with their performance on standardized examinations, personality type was associated with faculty evaluations of their performance.23 It is evident that a profound scientific grounding is necessary for a physician to be able to formulate a cogent management plan for an ill patient, and the successful clinician must be able to pass a certification examination. However, because computer systems become more and more adept, the scientific/technical components may be readily available and less dependent on the technical knowledge of the physician; the greater contribution of the caregiver will likely be leadership and human interaction. An ill or injured patient (and his or her relatives) not only wants understanding of the medical issue from a physician, but the patient also wants compassion, empathy, and caring. With the ever increasing complexity of clinical cases and increasing medical and technical knowledge,24 there is a tendency to overlook this critical human and humane relationship. In the field of anesthesiology, there are frequently situations where compassion and caring require coercive and/or pacesetting leadership rather than kindness and empathy, for example, during life-threatening A-, B-, C-, or D-problems according to ACLS or ATLS protocols. In such moments, emotionally intelligent anesthesiologists will be well aware of the pressure, yet will self-regulate, approach the situation with clarity, motivate their teams, and support a climate of respect even in highly stressful circumstances.25,26 In her milestone article, Diane Coutu27 described the properties of personalities with such down-to-earth behavior that not only embraced the "coolness" to accept harsh realities and the ability to realize "what matters for survival," but additionally to create meaning from them as "resilience." Since then, EI and adaptive coordination, resilience, and themes of reflective practice toward self-awareness, development of core values, and moral leadership have been described as fundamental goals in an active and constructive process of professional identity formation in medicine.28 Zwack et al asked "if every fifth physician is affected by burnout, what about the other four?" They found that focusing on positive aspects of work, "personal reflexivity," and accepting both personal and professional boundaries were resilience strategies employed by experienced physicians.29 In medicine, the recognition that resilience is a key to optimal performance has emerged only recently.30,31 Given the evidence from both business and medical science, the selection of team members is probably the critical task for leadership in anesthesiology32 and for patient safety.33 But the question remains: do psychological measurements gleaned from the interview process allow us to select individuals who know what really matters? If not, can we learn to select for personality types who can be taught what matters? CONCLUSIONS The available evidence suggests that EI is a desirable attribute for physicians in anesthesiology and acute care medicine. Anticipating the evolution of our specialty, it is plausible that emotionally intelligent anesthesiologists are more likely to be successful in the future health care environment. Accordingly, we advocate including an evaluation of EI in our resident selection process, as well as ongoing EI training throughout an anesthesiologist's career. EI is not soft kindness or unprofessional commiseration. It is the sine qua non of leadership. DISCLOSURES Name: Markus M. Luedi, MD, MBA. Contribution: This author helped write the manuscript. Name: Dietrich Doll, MD, PhD. Contribution: This author helped write the manuscript. Name: Steven D. Boggs, MD. Contribution: This author helped write the manuscript. Name: Frank Stueber, MD. Contribution: This author helped write the manuscript. This manuscript was handled by: Thomas R. Vetter, MD, MPH. Acting EIC on Final Acceptance: Thomas R. Vetter, MD, MPH.

Background: Dexamethasone is reported to induce both tumor-suppressive and tumor-promoting effects. The purpose of this study was to identify the genomic impact of dexamethasone in glioblastoma stem cell (GSC) lines and its prognostic value; furthermore, to identify drugs that can counter these side effects of dexamethasone exposure. Methods: We utilized 3 independent GSC lines with tumorigenic potential for this study. Whole-genome expression profiling and pathway analyses were done with dexamethasone-exposed and control cells. GSCs were also co-exposed to dexamethasone and temozolomide. Risk scores were calculated for most affected genes, and their associations with survival in The Cancer Genome Atlas and Repository of Molecular Brain Neoplasia Data databases. In silico Connectivity Map analysis identified camptothecin as antagonist to dexamethasone-induced negative effects. Results: Pathway analyses predicted an activation of dexamethasone network (z-score: 2.908). Top activated canonical pathways included “role of breast cancer 1 in DNA damage response” (P=1.07E–04). GSCs were protected against temozolomide-induced apoptosis when coincubated with dexamethasone. Altered cellular functions included cell movement, cell survival, and apoptosis with z-scores of 2.815, 5.137, and –3.122, respectively. CCAAT/enhancer binding protein beta (CEBPB) was activated in a dose dependent manner specifically in slow-dividing “stem-like” cells. CEBPB was activated in dexamethasone-treated orthotopic tumors. Patients with high risk scores had significantly shorter survival. Camptothecin was validated as potential partial neutralizer of dexamethasone-induced oncogenic effects. Conclusions: Dexamethasone exposure induces a genetic program and CEBPB expression in GSCs that adversely affects key cellular functions and response to therapeutics. High risk scores associated with these genes have negative prognostic value in patients. Our findings further suggest camptothecin as a potential neutralizer of adverse dexamethasone-mediated effects.

Editor, Patient safety is of utmost importance in anaesthesiology and has to be considered as a number one priority, also from a managerial point of view.1 Research, practice advisories and guidelines have tremendously improved perioperative patient safety over the last several decades. Anaesthesiologists have played a key role in these developments.2 High-reliability organisations, such as airlines, very quickly saw that qualitative factors (human factors) were just as important as quantitative factors, and were essential in the provision of the highest quality service. In 2007, a working group on Safety and Quality in Anaesthesiological Practice in the Section and Board of Anaesthesiology of the European Union of Medical Specialists (EUMS/UEMS) presented guidelines that also embraced legal aspects, audits and ethics.2 ‘Adaptive coordination’ has been shown to be a key characteristic of high-performing teams.3 The WHO surgical safety checklist, designed to improve teamwork, significantly reduced perioperative death rates.4 Chassin defined the elimination of ‘barriers to a strong and vibrant culture of safety’ as today's highest priority for healthcare leadership.5 Human resource practices and policies that support group orientation have been shown to directly affect the safety climate of organisations.6 Very recently, however, the tragedy in the French Alps caused by a psychologically disturbed pilot showed how dangerous a single team member can be if their behaviour is unstable and if their instability goes unrecognised by other team members and leadership. Comparable incidences in the healthcare setting, especially in acute care medicine, have happened and the number of unreported or undiscovered cases may presumably be high. Psychologically unstable staff members have induced patient damage or death multiple times. This airline catastrophe teaches us that the selection of team members is probably the critical task of leadership clearly going beyond that of ensuring safety provided by any guidelines and checklists. How to early identify those at risk in an interview situation as applicants or even at entry level as trainees? In addition, as psychotic or psychologically aberrant behaviour may occur throughout one's career, proven tools are needed to identify individuals and subsequently thereby prevent catastrophic incidents. How to then remove such members from duty will be a challenge going forward for both the airline industry and those in the operating suite. Acknowledgements relating to this article Assistance with the letter: none. Financial support and sponsorship: none. Conflicts of interest: none.

BACKGROUND: Evidence suggests that cannabinoids can prevent chemotherapy-induced nausea and vomiting. The use of tetrahydrocannabinol (THC) has also been suggested for the prevention of postoperative nausea and vomiting (PONV), but evidence is very limited and inconclusive. To evaluate the effectiveness of IV THC in the prevention of PONV, we performed this double-blind, randomized, placebo-controlled trial with patient stratification according to the risk of PONV. Our hypothesis was that THC would reduce the relative risk of PONV by 25% compared with placebo.METHODS: With IRB approval and written informed consent, 40 patients at high risk for PONV received either 0.125 mg/kg IV THC or placebo at the end of surgery before emergence from anesthesia. The primary outcome parameter was PONV during the first 24 hours after emergence. Secondary outcome parameters included early and late nausea, emetic episodes and PONV, and side effects such as sedation or psychotropic alterations.RESULTS: The relative risk reduction of overall PONV in the THC group was 12% (95% confidence interval, -37% to 43%), potentially less than the clinically significant 25% relative risk reduction demonstrated by other drugs used for PONV prophylaxis. Calculation of the effect of treatment group on overall PONV by logistic regression adjusted for anesthesia time gave an odds ratio of 0.97 (95% confidence interval, 0.21 to 4.43, P = 0.97). Psychotropic THC side effects were clinically relevant and mainly consisted of sedation and confusion that were not tampered by the effects of anesthesia. The study was discontinued after 40 patients because of the inefficacy of THC against PONV and the finding of clinically unacceptable side effects that would impede the use of THC in the studied setting.CONCLUSIONS: Because of an unacceptable side effect profile and uncertain antiemetic effects, IV THC administered at the end of surgery before emergence from anesthesia cannot be recommended for the prevention of PONV in high-risk patients.

Objective To investigate the periprocedural inflammatory response in patients with isolated aortic valve stenosis undergoing surgical aortic valve replacement (SAVR) or transcatheter aortic valve implantation (TAVI) with different technical approaches. Material and Methods Patients were prospectively allocated to one of the following treatments: SAVR using conventional extracorporeal circulation (CECC, n = 47) or minimized extracorporeal circulation (MECC, n = 15), or TAVI using either transapical (TA, n = 15) or transfemoral (TF, n = 24) access. Exclusion criteria included infection, pre-procedural immunosuppressive or antibiotic drug therapy and emergency indications. We investigated interleukin (IL)-6, IL-8, IL-10, human leukocyte antigen (HLA-DR), white blood cell count, high-sensitivity C-reactive protein (hs-CRP) and soluble L-selectin (sCD62L) levels before the procedure and at 4, 24, and 48 h after aortic valve replacement. Data are presented for group interaction (p-values for inter-group comparison) as determined by the Greenhouse-Geisser correction. Results SAVR on CECC was associated with the highest levels of IL-8 and hs-CRP (p<0.017, and 0.007, respectively). SAVR on MECC showed the highest descent in levels of HLA-DR and sCD62L (both p<0.001) in the perioperative period. TA-TAVI showed increased intraprocedural concentration and the highest peak of IL-6 (p = 0.017). Significantly smaller changes in the inflammatory markers were observed in TF-TAVI. Conclusion Surgical and interventional approaches to aortic valve replacement result in inflammatory modulation which differs according to the invasiveness of the procedure. As expected, extracorporeal circulation is associated with the most marked pro-inflammatory activation, whereas TF-TAVI emerges as the approach with the most attenuated inflammatory response. Factors such as the pre-treatment patient condition and the extent of myocardial injury also significantly affect inflammatory biomarker patterns. Accordingly, TA-TAVI is to be classified not as an interventional but a true surgical procedure, with inflammatory biomarker profiles comparable to those found after SAVR. Our study could not establish an obvious link between the extent of the periprocedural inflammatory response and clinical outcome parameters.