Activation of G protein-coupled estrogen receptor 1 ameliorates proximal tubular injury and proteinuria in Dahl salt-sensitive female rats.

Recent evidence indicates a crucial role for G protein-coupled estrogen receptor 1 (GPER1) in the maintenance of cardiovascular and kidney health in females. The current study tested whether GPER1 activation ameliorates hypertension and kidney damage in female Dahl salt-sensitive (SS) rats fed a high-salt (HS) diet. Adult female rats were implanted with telemetry transmitters for monitoring blood pressure and osmotic minipumps releasing G1 (selective GPER1 agonist, 400 µg/kg/day ip) or vehicle. Two weeks after pump implantation, rats were shifted from a normal-salt (NS) diet (0.4% NaCl) to a matched HS diet (4.0% NaCl) for 2 wk. Twenty-four hour urine samples were collected during both diet periods and urinary markers of kidney injury were assessed. Histological assessment of kidney injury was conducted after the 2-wk HS diet period. Compared with values during the NS diet, 24-h mean arterial pressure markedly increased in response to HS, reaching similar values in vehicle-treated and G1-treated rats. HS also significantly increased urinary excretion of protein, albumin, nephrin (podocyte damage marker), and KIM-1 (proximal tubule injury marker) in vehicle-treated rats. Importantly, G1 treatment prevented the HS-induced proteinuria, albuminuria, and increase in KIM-1 excretion but not nephrinuria. Histological analysis revealed that HS-induced glomerular damage did not differ between groups. However, G1 treatment preserved proximal tubule brush-border integrity in HS-fed rats. Collectively, our data suggest that GPER1 activation protects against HS-induced proteinuria and albuminuria in female Dahl SS rats by preserving proximal tubule brush-border integrity in a blood pressure-independent manner.

Acclimation to a High-Salt Diet Is Sex Dependent.

Background Premenopausal women are less likely to develop hypertension and salt-related complications than are men, yet the impact of sex on mechanisms regulating Na+ homeostasis during dietary salt challenges is poorly defined. Here, we determined whether female rats have a more efficient capacity to acclimate to increased dietary salt intake challenge. Methods and Results Age-matched male and female Sprague Dawley rats maintained on a normal-salt (NS) diet (0.49% NaCl) were challenged with a 5-day high-salt diet (4.0% NaCl). We assessed serum, urinary, skin, and muscle electrolytes; total body water; and kidney Na+ transporters during the NS and high-salt diet phases. During the 5-day high-salt challenge, natriuresis increased more rapidly in females, whereas serum Na+ and body water concentration increased only in males. To determine if females are primed to handle changes in dietary salt, we asked the question whether the renal endothelin-1 natriuretic system is more active in female rats, compared with males. During the NS diet, female rats had a higher urinary endothelin-1 excretion rate than males. Moreover, Ingenuity Pathway Analysis of RNA sequencing data identified the enrichment of endothelin signaling pathway transcripts in the inner medulla of kidneys from NS-fed female rats compared with male counterparts. Notably, in human subjects who consumed an Na+-controlled diet (3314-3668 mg/day) for 3 days, women had a higher urinary endothelin-1 excretion rate than men, consistent with our findings in NS-fed rats. Conclusions These results suggest that female sex confers a greater ability to maintain Na+ homeostasis during acclimation to dietary Na+ challenges and indicate that the intrarenal endothelin-1 natriuretic pathway is enhanced in women.

Preparing your intensive care unit to respond in crisis: considerations for critical care clinicians.

OBJECTIVE: In recent years, healthcare disaster planning has grown from its early place as an occasional consideration within the manuals of emergency medical services and emergency department managers to a rapidly growing field, which considers continuity of function, surge capability, and process changes across the spectrum of healthcare delivery. A detailed examination of critical care disaster planning was undertaken in 2007 by the Task Force for Mass Critical Care of the American College of Chest Physicians Critical Care Collaborative Initiative. We summarize the Task Force recommendations and available updated information to answer a fundamental question for critical care disaster planners: What is a prepared intensive care unit and how do I ensure my unit's readiness? DATA SOURCES: Database searches and review of relevant published literature. DATA SYNTHESIS: Preparedness is essential for successful response, but because intensive care units face many competing priorities, without defining "preparedness for what," the task can seem overwhelming. Intensive care unit disaster planners should, therefore, along with the entire hospital, participate in a hospital or regionwide planning process to 1) identify critical care response vulnerabilities; and 2) clarify the hazards for which their community is most at risk. The process should inform a comprehensive written preparedness plan targeting the most worrisome scenarios and including specific guidance on 1) optimal use of space, equipment, and staffing for delivery of critical care to significantly increased patient volumes; 2) allocation of resources for provision of essential critical care services under conditions of absolute scarcity; 3) intensive care unit evacuation; and 4) redundant internal communication systems and means for timely data collection. CONCLUSION: Critical care disaster planners have a complex, challenging task. Experienced planners will agree that no disaster response is perfect, but careful planning will enable the prepared intensive care unit to respond effectively in times of crisis.

Prevalence of SARS-CoV-2 Antibodies in a Multistate Academic Medical Center.

OBJECTIVE: To estimate the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in health care personnel. METHODS: The Mayo Clinic Serology Screening Program was created to provide a voluntary, two-stage testing program for SARS-CoV-2 antibodies to health care personnel. The first stage used a dried blood spot screening test initiated on June 15, 2020. Those participants identified as reactive were advised to have confirmatory testing via a venipuncture. Venipuncture results through August 8, 2020, were considered. Consent and authorization for testing was required to participate in the screening program. This report, which was conducted under an institutional review board-approved protocol, only includes employees who have further authorized their records for use in research. RESULTS: A total of 81,113 health care personnel were eligible for the program, and of these 29,606 participated in the screening program. A total of 4284 (14.5%) of the dried blood spot test results were "reactive" and warranted confirmatory testing. Confirmatory testing was completed on 4094 (95.6%) of the screen reactive with an overall seroprevalence rate of 0.60% (95% CI, 0.52% to 0.69%). Significant variation in seroprevalence was observed by region of the country and age group. CONCLUSION: The seroprevalence for SARS-CoV-2 antibodies through August 8, 2020, was found to be lower than previously reported in other health care organizations. There was an observation that seroprevalence may be associated with community disease burden.

Planning for the inevitable: preparing for epidemic and pandemic respiratory illness in the shadow of H1N1 influenza.

The recent outbreak of novel H1N1 influenza has underscored the importance of hospital preparedness in responding toepidemic and pandemic respiratory illness. Comprehensive planning for the emergence of novel respiratory pathogens shouldbe based on an all-hazards approach, with the input of key stakeholders. A staged, scalable model allows for a flexibleresponse, and the addition of a medical control chief and a situational assessment chief to the incident command systemprovides the clinical and epidemiologic expertise essential for effective implementation. Strategies for coordinated and efficientcommunication both within and outside the institution should be clearly outlined. Furthermore, the outbreak of novel H1N1influenza demonstrated the necessity of (1) additional support roles within the hospital, (2) development of employeedatabases, and (3) incorporation of disease severity into staged planning. Careful consideration of these issues will allowinstitutions to better meet the challenges of treating epidemic and pandemic respiratory illness, both now and in the future.

Infection control in mass respiratory failure: preparing to respond to H1N1.

The first hints of a global public health crisis emerged with the identification of a new strain of H1N1 influenza A in March and April 2009 in Mexico City. By June 11, the World Health Organization had declared the outbreak of 2009 H1N1 a global pandemic. Now, with the continued growing presence of 2009 H1N1 on the global scene, much attention has been focused on the key role of personal protective equipment in healthcare infection control. Much less emphasis has been placed on specific interventions that may minimize the increased infectious risk commonly associated with critical care delivery. Given the frequency of high-risk respiratory procedures such as intubation and delivery of aerosolized medications in the intensive care unit, the delivery of critical care presents unique infection control challenges and unique opportunities to augment usual infection control practice with specific source-control efforts. Here, we summarize data regarding risks to critical care healthcare workers from previous respiratory virus outbreaks, discuss findings from the early 2009 H1N1 experience that suggest reasons for increased concern for those delivering critical care, and review best available evidence regarding strategies for source control in respiratory and critical care delivery.

Evidence for G-Protein-Coupled Estrogen Receptor as a Pronatriuretic Factor.

Background The novel estrogen receptor, G-protein-coupled estrogen receptor (GPER), is responsible for rapid estrogen signaling. GPER activation elicits cardiovascular and nephroprotective effects against salt-induced complications, yet there is no direct evidence for GPER control of renal Na+ handling. We hypothesized that GPER activation in the renal medulla facilitates Na+ excretion. Methods and Results Herein, we show that infusion of the GPER agonist, G1, to the renal medulla increased Na+ excretion in female Sprague Dawley rats, but not male rats. We found that GPER mRNA expression and protein abundance were markedly higher in outer medullary tissues from females relative to males. Blockade of GPER in the renal medulla attenuated Na+ excretion in females. Given that medullary endothelin 1 is a well-established natriuretic factor that is regulated by sex and sex steroids, we hypothesized that GPER activation promotes natriuresis via an endothelin 1-dependent pathway. To test this mechanism, we determined the effect of medullary infusion of G1 after blockade of endothelin receptors. Dual endothelin receptor subtype A and endothelin receptor subtype B antagonism attenuated G1-induced natriuresis in females. Unlike males, female mice with genetic deletion of GPER had reduced endothelin 1, endothelin receptor subtype A, and endothelin receptor subtype B mRNA expression compared with wild-type controls. More important, we found that systemic GPER activation ameliorates the increase in mean arterial pressure induced by ovariectomy. Conclusions Our data uncover a novel role for renal medullary GPER in promoting Na+ excretion via an endothelin 1-dependent pathway in female rats, but not in males. These results highlight GPER as a potential therapeutic target for salt-sensitive hypertension in postmenopausal women.

The use of personal protective equipment for control of influenza among critical care clinicians: A survey study.

BACKGROUND: Intensive care units (ICUs) are potential high-risk areas for transmission of viruses causing febrile respiratory illness, such as influenza. Healthcare-associated influenza is prevented through healthcare worker (HCW) vaccination and effective use of U.S. Centers for Disease Control and Prevention recommended infection control practices, including use of personal protective equipment (PPE). Although effective PPE use may significantly reduce healthcare-associated influenza transmission, PPE adherence among ICU HCWs for preventing nosocomial influenza infection has not been evaluated. OBJECTIVE: To characterize ICU HCW behavior, knowledge, and attitudes about recommended precautions for the prevention of healthcare-associated influenza infections. DESIGN, SETTING, AND PARTICIPANTS: A survey of 292 internal medicine housestaff, pulmonary/critical care fellows and faculty, nurses, and respiratory care professionals working in four ICUs in two hospitals in Baltimore, MD. MEASUREMENTS AND MAIN RESULTS: Of those surveyed, 88% (n = 256) completed the survey. Only 63% of respondents were able to correctly identify adequate influenza PPE, and 62% reported high adherence (>80%) with PPE use for prevention of nosocomial influenza. In multivariable modeling, odds of high adherence varied by clinician type. Respondents who believed adherence was inconvenient had lower odds of high adherence (odds ratio 0.42, 95% confidence interval 0.22-0.82), and those reporting likelihood of being reprimanded for nonadherence were more likely to adhere (odds ratio 2.40, 95% confidence interval 1.25-4.62). CONCLUSIONS: ICU HCWs report suboptimal levels of influenza PPE adherence. This finding in a high-risk setting is particularly concerning, given that it likely overestimates actual behavior. Both suboptimal adherence levels and significant PPE knowledge gaps indicate that ICU HCWs may be at a substantial risk of developing and/or transmitting nosocomial respiratory viral infection. Improving respiratory virus infection control will likely require closing knowledge gaps and changing organizational factors that influence behavior.

Health care worker protection in mass casualty respiratory failure: infection control, decontamination, and personal protective equipment.

Maintenance of a safe and stable health care infrastructure is critical to an effective mass casualty disaster response. Both secondary contamination during chemical disasters and hospital-associated infections during epidemic illness can pose substantial threats to achieving this goal. Understanding basic principles of decontamination and infection control during responses to chemical and biologic disasters can help minimize the risks to patients and health care workers. Effective decontamination following toxic chemical exposure should include both removal of contaminated clothing and decontamination of the victim's skin. Wet decontamination is the most feasible strategy in a mass casualty situation and should be performed promptly by trained personnel. In the event of an epidemic, infection prevention and control measures are based on essential principles of hand hygiene and standard precautions. Expanded precautions should be instituted as needed to target contact, droplet, and airborne routes of infectious disease transmission. Specific equipment and measures for critical care delivery may serve to decrease risk to health care workers in the event of an epidemic. Their use should be considered in developing comprehensive disaster response plans.

Surge capacity mechanical ventilation.

Mechanical ventilation in a situation of mass casualty respiratory failure will require a substantial increase in the capacity for mechanical ventilation, to prevent unnecessary mortality. Concern over the difficulties of treating large numbers of patients with respiratory failure is exceeded only by our lack of experience on which to base decisions. This review evaluates the likely scenarios that could lead to mass casualty respiratory failure and the types of respiratory failure anticipated. A literature review was conducted, using the National Library of Medicine Medical Subject Headings terms "mass casualty respiratory failure," "pandemic flu," "disaster preparedness," and "mass casualty care." Papers were reviewed for relevance to the topic. There is little historical or empirical evidence upon which to base decisions regarding mass casualty respiratory failure and augmenting positive-pressure ventilation capacity. Matching the degree of respiratory impairment anticipated from the most likely mass casualty scenarios allows conclusions to be drawn regarding the performance characteristics of ventilators required for these situations. Little is known about the success of mechanical-ventilator stockpiling for mass casualty respiratory failure. Careful planning with an emphasis on matching ventilator performance to patient need and caregiver skill is critical to appropriate stockpile choices.

Ventilator-associated pneumonia: overdiagnosis and treatment are common in medical and surgical intensive care units.

OBJECTIVE: Diagnosing ventilator-associated pneumonia (VAP) is difficult, and misdiagnosis can lead to unnecessary and prolonged antibiotic treatment. We sought to quantify and characterize unjustified antimicrobial use for VAP and identify risk factors for continuation of antibiotics in patients without VAP after 3 days. METHODS: Patients suspected of having VAP were identified in 6 adult intensive care units (ICUs) over 1 year. A multidisciplinary adjudication committee determined whether the ICU team's VAP diagnosis and therapy were justified, using clinical, microbiologic, and radiographic data at diagnosis and on day 3. Outcomes included the proportion of VAP events misdiagnosed as and treated for VAP on days 1 and 3 and risk factors for the continuation of antibiotics in patients without VAP after day 3. RESULTS: Two hundred thirty-one events were identified as possible VAP by the ICUs. On day 1, 135 (58.4%) of them were determined to not have VAP by the committee. Antibiotics were continued for 120 (76%) of 158 events without VAP on day 3. After adjusting for acute physiology and chronic health evaluation II score and requiring vasopressors on day 1, sputum culture collection on day 3 was significantly associated with antibiotic continuation in patients without VAP. Patients without VAP or other infection received 1,183 excess days of antibiotics during the study. CONCLUSIONS: Overdiagnosis and treatment of VAP was common in this study and led to 1,183 excess days of antibiotics in patients with no indication for antibiotics. Clinical differences between non-VAP patients who had antibiotics continued or discontinued were minimal, suggesting that clinician preferences and behaviors contribute to unnecessary prescribing.

Perceptions and influence of a hospital influenza vaccination policy.

OBJECTIVE: Seasonal influenza is a significant cause of morbidity and mortality in the United States each year. Healthcare worker (HCW) influenza vaccination is associated with both decreased absenteeism among employees and improved outcomes among patients. However, HCW influenza vaccine uptake remains suboptimal. The objective of this study was to characterize HCWs' understanding of and response to a stringent vaccination policy. DESIGN, SETTING, AND PARTICIPANTS: A survey of 928 hospital staff at a tertiary academic medical center in Baltimore during the 2008-2009 influenza season. RESULTS: Of those surveyed, 75% (n = 695) completed the survey; 623 respondents reported regular patient contact, and 91% of those reported vaccination in the current influenza season. However, only 60% reported consistently receiving the vaccine every year. Of those who were vaccinated, 8% (n = 48) reported being vaccinated for the first time during that influenza season. A significant proportion (42%) of respondents were unaware of the major change in hospital policy regarding vaccination. Influences on the decision to be vaccinated varied significantly between those who are regularly vaccinated and those with inconsistent vaccination habits. Attitudes toward hospital policy varied significantly by race and clinical role. CONCLUSIONS: Although 91% of respondents with regular patient contact reported being vaccinated for influenza in the 2008-2009 season, only 60% reported consistent annual vaccination. Misinformation regarding hospital policies is widespread. Improvements in vaccination rates will likely require multifaceted, targeted efforts focused on specific influences on less adherent groups. The identified variability in influences on the decision to be vaccinated suggests possible targets for future interventions.

Survey study of the knowledge, attitudes, and expected behaviors of critical care clinicians regarding an influenza pandemic.

OBJECTIVE: Intensive care units (ICUs) are potential high-risk areas for the transmission of respiratory viruses such as influenza. An influenza pandemic is expected to result in a dramatic surge of critically ill patients, and ICU healthcare workers (HCW) are likely to be at high risk of infection. OBJECTIVE: To characterize the knowledge, attitudes, and expected behaviors of ICU HCWs concerning the risk of and response to an influenza pandemic. DESIGN, PARTICIPANTS, AND SETTING: A survey was distributed to 292 HCWs (ie, internal medicine house staff, pulmonary and critical care fellows and faculty members, nurses, and respiratory care professionals) at 2 hospitals in Baltimore, Maryland. RESULTS: Of the 292 HCWs, 256 (88%) completed the survey. Just over one-half of the respondents believed there is at least a 45% chance of an influenza pandemic within the next 5 years. However, only 41% reported knowing how to protect themselves during an outbreak. Despite this common belief that a pandemic is likely in the near future, 59% of those surveyed reported only minimal knowledge of the risks of and protective strategies for an influenza pandemic, and 20% reported being unlikely to report to work during a pandemic or being unsure about whether they would do so. The odds of reporting to work varied on the basis of race and responsibility for child care. CONCLUSIONS: ICU HCWs reported having minimal knowledge concerning the risk of and response to an influenza pandemic, even though more that one-half of HCWs expect that a pandemic will occur in the near future. This finding in a high-risk setting is of concern, given that lack of knowledge among HCWs may result in increased nosocomial transmission to HCWs and patients. Interventions to improve knowledge of pandemics and understanding of risks among ICU HCWs are essential.

Recognition and importance of forced exhalation on the measurement of intraabdominal pressure: a subgroup analysis from a prospective cohort study on the incidence of abdominal compartment syndrome in medical patients.

Intraabdominal pressure is measured conventionally at end-expiration; however, the significance of forced exhalation on this measurement has not been evaluated previously. Using data from a previous prospective cohort study of the incidence of intraabdominal hypertension and abdominal compartment syndrome in medical intensive care unit patients, the authors evaluated 65 strip-chart recordings obtained from 28 patients who had measurements of intraabdominal pressure and airway pressures taken simultaneously. Forced exhalation was identified by a rise in intraabdominal pressure during exhalation. Forced exhalation was observed in 4 patients; with a mean intraabdominal pressure increase of 14.3 +/- 1.3 mm Hg at end-exhalation, compared with a decrease of -2.5 +/- 1.2 mm Hg in 24 patients without forced exhalation and absolute pressures of 28.0 +/- 6.6 versus 13.8 +/- 3.9 mm Hg (P < .001). However, there was no difference in end-inspiratory values. Forced exhalation is not uncommon in acutely ill, mechanically ventilated medical intensive care unit patients and may increase intraabdominal pressure significantly to values that exceed the diagnostic threshold for abdominal compartment syndrome.

Mass casualty respiratory failure.

PURPOSE OF REVIEW: The severe acute respiratory syndrome epidemic of 2002-2003, recent natural catastrophes, burgeoning concerns regarding intentional catastrophes, and the looming threat of an influenza pandemic have focused attention on large-scale, survivable respiratory failure. In this article, we review appropriate medical equipment, treatment space, and strategies to augment health professional staff in response to a massive increase in need for sustained critical care. RECENT FINDINGS: There is insufficient modern healthcare experience with mass casualty respiratory failure to develop evidence-based preparedness efforts. For this reason, initial efforts to augment critical care capability in response to disasters have relied on extrapolation from the routine critical care knowledge base, military medicine, critical care transport, and expert opinion. We review recently published documents on augmenting supplies of positive pressure ventilation equipment, ongoing projects for increasing health professional staff, and infection control issues during epidemics. SUMMARY: Mass casualty respiratory failure remains a largely unstudied field, but we believe informed decisions about equipment stockpiling and use, the development of creative operational concepts to increase staffing, and the careful implementation of rational infection control practices can lay a foundation for an appropriate response until additional data become available.

Abdominal compartment syndrome is common in medical intensive care unit patients receiving large-volume resuscitation.

Intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) have been well described in surgical patients. Large-volume resuscitation is thought to be a risk factor for IAH/ACS in this group. However, little is known of the incidence of IAH/ACS in critically ill medical patients. The authors aim to ascertain the incidence of ACS in critically ill medical patients receiving large-volume resuscitation. Over an 8-month study period, the authors performed a prospective cohort study of medical intensive care unit (ICU) patients with a minimum net positive fluid balance of 5 L within the preceding 24 hours. The primary outcome of interest is the development of ACS, defined as an intra-abdominal pressure (IAP) > or = 20 mm Hg associated with new organ dysfunction. IAP was measured by transducing bladder pressure and was recorded along with fluid balance at enrollment and every 12 hours thereafter up to 96 hours. The setting is a medical ICU at a major university hospital. Of the 468 medical ICU admissions screened, 40 (8.5%) were identified who met the 24-hour fluid balance inclusion criterion. Upon enrollment, this cohort had a mean Acute Physiology And Chronic Health Evaluation II score of 23 and a median positive fluid balance of 6.9 L. Thirty-four of the 40 study patients (85%) had intra-abdominal hypertension (IAP > or = 12 mm Hg). During the study period, 13 of the 40 (33%) patients developed IAP > or = 20 mm Hg and 10 (25%) met the criteria for ACS. None underwent laparotomy. ACS is frequently found in critically ill medical patients receiving large-volume resuscitation. The clinical significance of this finding remains unclear. However, routine monitoring of IAP should be considered in medical patients with a 5-L net positive fluid balance in 24 hours. Future studies are warranted to evaluate clinical outcomes of medical patients with ACS and risk factors for its development.