APOL1 risk variants in individuals of African genetic ancestry drive endothelial cell defects that exacerbate sepsis.

The incidence and severity of sepsis is higher among individuals of African versus European ancestry. We found that genetic risk variants (RVs) in the trypanolytic factor apolipoprotein L1 (APOL1), present only in individuals of African ancestry, were associated with increased sepsis incidence and severity. Serum APOL1 levels correlated with sepsis and COVID-19 severity, and single-cell sequencing in human kidneys revealed high expression of APOL1 in endothelial cells. Analysis of mice with endothelial-specific expression of RV APOL1 and in vitro studies demonstrated that RV APOL1 interfered with mitophagy, leading to cytosolic release of mitochondrial DNA and activation of the inflammasome (NLRP3) and the cytosolic nucleotide sensing pathways (STING). Genetic deletion or pharmacological inhibition of NLRP3 and STING protected mice from RV APOL1-induced permeability defects and proinflammatory endothelial changes in sepsis. Our studies identify the inflammasome and STING pathways as potential targets to reduce APOL1-associated health disparities in sepsis and COVID-19.

Transcriptomic responses of peripheral blood leukocytes to cardiac surgery after acute inflammation, and three months recovery.

Traumatic perioperative conditions may trigger early systemic responses, activate leukocytes and reprogram the immune system. We hypothesize that leukocyte activation may not revert to pre-surgical states, and that protracted activation may emerge with increased risks of comorbidities. We tested this concept by examining the transcriptomes of monocytes and T cells in a representative observational cohort of patients (n = 13) admitted for elective cardiac surgery. Transcriptomes in T cells and monocytes were compared from before surgery (t0), and monocytes were analyzed longitudinally after acute (t24hr), and convalescent (t3m) time points. Monocytes and T cells expressed distinct transcriptomes, reflected by statistically significant differential expression of 558 T cell related genes. Monocytes expressed genes related to protein degradation and presented atypical activation of surface markers and cytoplasmic functions over time. Additionally, monocytes exhibited limited transcriptomic heterogeneity prior to surgery, and long-term patterns of gene expression associated with atherosclerosis showed three temporally distinct signatures. These data establish that post-cardiac surgery transcriptomes of monocytes differ even at three months compared to baselines, which may reflect latent ('smoldering') inflammation and persistent progression of tissue degenerative processes that should inform clinical care.

Safety, feasibility, and impact on the gut microbiome of kefir administration in critically ill adults.

BACKGROUND: Dysbiosis of the gut microbiome is frequent in the intensive care unit (ICU), potentially leading to a heightened risk of nosocomial infections. Enhancing the gut microbiome has been proposed as a strategic approach to mitigate potential adverse outcomes. While prior research on select probiotic supplements has not successfully shown to improve gut microbial diversity, fermented foods offer a promising alternative. In this open-label phase I safety and feasibility study, we examined the safety and feasibility of kefir as an initial step towards utilizing fermented foods to mitigate gut dysbiosis in critically ill patients. METHODS: We administered kefir in escalating doses (60 mL, followed by 120 mL after 12 h, then 240 mL daily) to 54 critically ill patients with an intact gastrointestinal tract. To evaluate kefir's safety, we monitored for gastrointestinal symptoms. Feasibility was determined by whether patients received a minimum of 75% of their assigned kefir doses. To assess changes in the gut microbiome composition following kefir administration, we collected two stool samples from 13 patients: one within 72 h of admission to the ICU and another at least 72 h after the first stool sample. RESULTS: After administering kefir, none of the 54 critically ill patients exhibited signs of kefir-related bacteremia. No side effects like bloating, vomiting, or aspiration were noted, except for diarrhea in two patients concurrently on laxatives. Out of the 393 kefir doses prescribed for all participants, 359 (91%) were successfully administered. We were able to collect an initial stool sample from 29 (54%) patients and a follow-up sample from 13 (24%) patients. Analysis of the 26 paired samples revealed no increase in gut microbial α-diversity between the two timepoints. However, there was a significant improvement in the Gut Microbiome Wellness Index (GMWI) by the second timepoint (P = 0.034, one-sided Wilcoxon signed-rank test); this finding supports our hypothesis that kefir administration can improve gut health in critically ill patients. Additionally, the known microbial species in kefir were found to exhibit varying levels of engraftment in patients' guts. CONCLUSIONS: Providing kefir to critically ill individuals is safe and feasible. Our findings warrant a larger evaluation of kefir's safety, tolerability, and impact on gut microbiome dysbiosis in patients admitted to the ICU. TRIAL REGISTRATION: NCT05416814; trial registered on June 13, 2022.

Immunological Signatures in Blood and Urine in 80 Individuals Hospitalized during the Initial Phase of COVID-19 Pandemic with Quantified Nicotine Exposure.

This research analyzes immunological response patterns to SARS-CoV-2 infection in blood and urine in individuals with serum cotinine-confirmed exposure to nicotine. Samples of blood and urine were obtained from a total of 80 patients admitted to hospital within 24 h of admission (tadm), 48 h later (t48h), and 7 days later (t7d) if patients remained hospitalized or at discharge. Serum cotinine above 3.75 ng/mL was deemed as biologically significant exposure to nicotine. Viral load was measured with serum SARS-CoV-2 S-spike protein. Titer of IgG, IgA, and IgM against S- and N-protein assessed specific antiviral responses. Cellular destruction was measured by high mobility group box protein-1 (HMGB-1) serum levels and heat shock protein 60 (Hsp-60). Serum interleukin 6 (IL-6), and ferritin gauged non-specific inflammation. The immunological profile was assessed with O-link. Serum titers of IgA were lower at tadm in smokers vs. nonsmokers (p = 0.0397). IgM at t48h was lower in cotinine-positive individuals (p = 0.0188). IgG did not differ between cotinine-positive and negative individuals. HMGB-1 at admission was elevated in cotinine positive individuals. Patients with positive cotinine did not exhibit increased markers of non-specific inflammation and tissue destruction. The blood immunological profile had distinctive differences at admission (MIC A/B↓), 48 h (CCL19↓, MCP-3↓, CD28↑, CD8↓, IFNγ↓, IL-12↓, GZNB↓, MIC A/B↓) or 7 days (CD28↓) in the cotinine-positive group. The urine immunological profile showed a profile with minimal overlap with blood as the following markers being affected at tadm (CCL20↑, CXCL5↑, CD8↑, IL-12↑, MIC A/B↑, GZNH↑, TNFRS14↑), t48h (CCL20↓, TRAIL↓) and t7d (EGF↑, ADA↑) in patients with a cotinine-positive test. Here, we showed a distinctive immunological profile in hospitalized COVID-19 patients with confirmed exposure to nicotine.

Elevated Serum Fibroblast Growth Factor 23 (FGF-23) Perseveres into a Convalescence Period After Elective Cardiac Surgery, with Receptor Activator of Nuclear Factor κB Ligand (RANKL) and Cartilage Oligomeric Matrix Protein (COMP) Being Part of the Peri-Surgical -Pro-Arteriosclerotic Inflammatory Response.

BACKGROUND Receptor activator of nuclear factor kappa B ligand (RANKL), osteoprotegerin (OPG), cartilage oligomeric matrix protein (COMP), bone morphogenetic protein (BMP-2), and fibroblast growth factor 23 (FGF-23) are involved in inflammation, calcium deposition, and fibrosis of blood vessels. Acute changes in these factors may contribute to the progression of arteriosclerosis, especially if their elevated serum levels persist postoperatively. MATERIAL AND METHODS A total of 90 patients (79 White, 4 African American, and 7 Other) undergoing elective heart surgery were enrolled in the study. Blood was collected before surgery and after surgery at 24 hours, 7 days, and 3 months to allow for longitudinal comparisons. After the plasma isolation, several biomarkers levels were studied using an enzymatic-linked assay. Demographic and clinical information were obtained from electronic health records. RESULTS At 24 hours after surgery, RANKL (RANKLbaseline=248.7±215.7 vs RANKLt24h=376.4±329.7; P=0.035), and BMP-2 (BMP-2baseline=283.7±255.4 vs BMP-2t24h=482.4; P=0.015) were significantly elevated compared to baseline, with levels returning to baseline at 7 days. FGF-23 increased significantly from baseline (FGF-23baseline=1020±1210) to 7 days (FGF-237d=2191±5188; P=0.029) and remained significantly higher than baseline at 3 months (FGF-233m=2041±3521; P=0.044). White blood cells (WBC) remained elevated at discharge (WBCbaseline=6.8±2.1 vs WBC24h=15.0±5.3 vs WBCdischarge=8.8±3.4). IL-8 and C-reactive protein normalized at 3 months. Estimated blood loss was significantly correlated with RANKL at 24 hours (r²=0.33; P=0.035). Serum creatinine levels after surgery at 24 hours (r²=0.41; p=0.008) and 7 days (r²=0.59; P=0.000) was strongly correlated with COMP. CONCLUSIONS Persistent elevation of serum FGF-23 indicates a potential for accelerated arteriosclerosis after cardiac surgery.

Cortical Spreading Depolarization and Delayed Cerebral Ischemia; Rethinking Secondary Neurological Injury in Subarachnoid Hemorrhage.

Poor outcomes in Subarachnoid Hemorrhage (SAH) are in part due to a unique form of secondary neurological injury known as Delayed Cerebral Ischemia (DCI). DCI is characterized by new neurological insults that continue to occur beyond 72 h after the onset of the hemorrhage. Historically, it was thought to be a consequence of hypoperfusion in the setting of vasospasm. However, DCI was found to occur even in the absence of radiographic evidence of vasospasm. More recent evidence indicates that catastrophic ionic disruptions known as Cortical Spreading Depolarizations (CSD) may be the culprits of DCI. CSDs occur in otherwise healthy brain tissue even without demonstrable vasospasm. Furthermore, CSDs often trigger a complex interplay of neuroinflammation, microthrombi formation, and vasoconstriction. CSDs may therefore represent measurable and modifiable prognostic factors in the prevention and treatment of DCI. Although Ketamine and Nimodipine have shown promise in the treatment and prevention of CSDs in SAH, further research is needed to determine the therapeutic potential of these as well as other agents.

Postoperative Dynamic of Leptin and Fibroblast Growth Factor 21 in 123 Patients Recovering from Cardiac Surgery.

BACKGROUND Cardiac surgery triggers acute changes in serum leptin and fibroblast growth factor 21 (FGF-21). Considering their pleiotropic role in inflammation and abnormal glucose metabolism, perseverance of their abnormal serum level can have a long-term impact on recovery and end-organ failures. Long-term dynamics after cardiac surgery are unknown. MATERIAL AND METHODS Serum was collected from 123 patients before cardiac surgery (tbaseline) and 24 h (t24h), 7 days (t7d), and 3 months (t3m) later. Also, interleukin 6 (IL-6) and C-reactive protein (CRP) assessed nonspecific inflammatory responses. Neurodegeneration was gauged with serum amyloid ß1-40 and ß1-42. Demographic and clinical information, including disposition at 28 days and t3m from admission, were collected. RESULTS Serum leptin increased at t24h (leptinbaseline=613+747.9 vs leptin24h=768±718.1; P=0.0083) and decreased at t7d (leptin7d=499.5±540.2; P=0.043). FGF-21 levels increased at t24h and t7d. Cytokines normalized by t3m. Presurgical leptin levels were higher in Asians and were the primary determinant of postoperative leptin changes. Leptin levels were most elevated in patients undergoing aortic valve and arch surgery; the perioperative increase was significant only in patients with mitral valve surgery. Leptin and FGF-21 did not correlate with markers of general inflammation (CRP, IL-6), which partially resolved after t3m. Amyloid ß1-42 at t3m correlated with leptin peak at t24h. Low prehospital FGF-21 level correlated with the incidence of perioperative stroke; postoperative FGF-21 correlated with discharge to facility vs home. CONCLUSIONS Leptin and FGF-21 evolve independently from the inflammatory response in the aftermath of cardiac surgery and correlate with cardiac remodeling and neurodegeneration markers.

Pilot of rapid implementation of the advanced practice provider in the workflow of an existing tele-critical care program.

Incorporating the advanced practice provider (APP) in the delivery of tele critical care medicine (teleCCM) addresses the critical care provider shortage. However, the current literature lacks details of potential workflows, deployment difficulties and implementation outcomes while suggesting that expanding teleCCM service may be difficult. Here, we demonstrate the implementation of a telemedicine APP (eAPP) pilot service within an existing teleCCM program with the objective of determining the feasibility and ease of deployment. The goal is to augment an existing tele-ICU system with a balanced APP service to assess the feasibility and potential impact on the ICU performance in several hospitals affiliated within a large academic center. A REDCap survey was used to assess eAPP workflows, expediency of interventions, duration of tasks, and types of assignments within different service locations. Between 02/01/2021 and 08/31/2021, 204 interventions (across 133 12-h shift) were recorded by eAPP (nroutine = 109 (53.4%); nurgent = 82 (40.2%); nemergent = 13 (6.4%). The average task duration was 10.9 ± 6.22 min, but there was a significant difference based on the expediency of the task (F [2; 202] = 3.89; p < 0.022) and type of tasks (F [7; 220] = 6.69; p < 0.001). Furthermore, the eAPP task type and expediency varied depending upon the unit engaged and timeframe since implementation. The eAPP interventions were effectively communicated with bedside staff with only 0.5% of suggestions rejected. Only in 2% cases did the eAPP report distress. In summary, the eAPP can be rapidly deployed in existing teleCCM settings, providing adaptable and valuable care that addresses the specific needs of different ICUs while simultaneously enhancing the delivery of ICU care. Further studies are needed to quantify the input more robustly.

Communication and role clarity inform TeleICU use: a qualitative analysis of opportunities and barriers in an established program using AACN framework.

BACKGROUND: Understanding the use of tele-intensive care unit (ICU) services is an essential component in evaluating current practice and informing future use as the adoption and application of teleICU services expands. We sought to explore if novel ways to utilize teleICU services can emerge within an established, consulting-style teleICU model considering the program's flexible, provider-driven operation. METHODS: This was a qualitative study of one teleICU/hospital dyad using semi-structured interviews from a convenience sample of ICU (n = 19) and teleICU (n = 13) nurses. Interviews were analyzed using directed content analysis to identify themes that describe their experiences with teleICU using a deductive codebook developed from an expert consensus (American Association of Critical Care Nurses) AACN statement on teleICU nursing. RESULTS: Three themes were identified through the qualitative content analysis: [1] nurses described unique teleICU knowledge, including systems thinking and technological skills, [2] the teleICU partnership supported quality improvement initiatives, and [3] elements of the work environment influenced perceptions of teleICU and its use. When elements of the work environment, such as effective communication and role clarity, were not present, teleICU use was variable. CONCLUSIONS: Flexible, provider-driven approaches for integrating teleICU services into daily practice may help define the future use of the teleICU model's applicability. Future work should focus on the importance of effective communication and role clarity in integrating the emerging teleICU services into teleICU/ICU practice.

Persistence of Lipoproteins and Cholesterol Alterations after Sepsis: Implication for Atherosclerosis Progression.

(1) Background: Sepsis is one of the most common critical care illnesses with increasing survivorship. The quality of life in sepsis survivors is adversely affected by several co-morbidities, including increased incidence of dementia, stroke, cardiac disease and at least temporary deterioration in cognitive dysfunction. One of the potential explanations for their progression is the persistence of lipid profile abnormalities induced during acute sepsis into recovery, resulting in acceleration of atherosclerosis. (2) Methods: This is a targeted review of the abnormalities in the long-term lipid profile abnormalities after sepsis; (3) Results: There is a well-established body of evidence demonstrating acute alteration in lipid profile (HDL-c ↓↓, LDL-C -c ↓↓). In contrast, a limited number of studies demonstrated depression of HDL-c levels with a concomitant increase in LDL-C -c in the wake of sepsis. VLDL-C -c and Lp(a) remained unaltered in few studies as well. Apolipoprotein A1 was altered in survivors suggesting abnormalities in lipoprotein metabolism concomitant to overall lipoprotein abnormalities. However, most of the studies were limited to a four-month follow-up and patient groups were relatively small. Only one study looked at the atherosclerosis progression in sepsis survivors using clinical correlates, demonstrating an acceleration of plaque formation in the aorta, and a large metanalysis suggested an increase in the risk of stroke or acute coronary event between 3% to 9% in sepsis survivors. (4) Conclusions: The limited evidence suggests an emergence and persistence of the proatherogenic lipid profile in sepsis survivors that potentially contributes, along with other factors, to the clinical sequel of atherosclerosis.

Humanized Mice as a Tool to Study Sepsis-More Than Meets the Eye.

(1) Background. Repetitive animal studies that have disappointed upon translation into clinical therapies have led to an increased appreciation of humanized mice as a remedy to the shortcomings of rodent-based models. However, their limitations have to be understood in depth. (2) Methods. This is a narrative, comprehensive review of humanized mice and sepsis literature to understand the model's benefits and shortcomings. (3) Results: Studies involving humanized models of sepsis include bacterial, viral, and protozoan etiology. Humanized mice provided several unique insights into the etiology and natural history of sepsis and are particularly useful in studying Ebola, and certain viral and protozoan infections. However, studies are relatively sparse and based on several different models of sepsis and humanized animals. (4) Conclusions. The utilization of humanized mice as a model for sepsis presents complex limitations that, once surpassed, hold some potential for the advancement of sepsis etiology and treatment.

Prolonged Transcriptional Consequences in Survivors of Sepsis.

Survivors of sepsis often suffer from prolonged post-critical illness syndrome secondary to the immune system's reprogramming. It is unclear if this process is static and pervasive due to methodological difficulties studying long-term outcomes of sepsis. The purpose of this study is to evaluate transcriptional profiles longitudinally in Drosophila melanogaster in the aftermath of sepsis to provide preliminary data for targets playing a role in post-sepsis immunostasis. Adult Drosophila melanogaster were infected with E. coli, and survivors were euthanized at 7, 14, and 21 days. Control flies were subjected to sham stress. Gene profiling was done with RNA-seq, and potential miRNA factors were computed. Profiling identified 55 unique genes at seven days, 61 unique genes at 14 days, and 78 genes at 21 days in sepsis survivors vs. sham control. Each post-sepsis timepoint had a distinctive transcriptional pattern with a signature related to oxidative stress at seven days, neuronal signal transduction at 14 days, and metabolism at 21 days. Several potential miRNA patterns were computed as potentially affecting several of the genes expressed in sepsis survivors. Our study demonstrated that post-sepsis changes in the transcriptome profile are dynamic and extend well into the Drosophila melanogaster natural life span.

Tele-Critical Care: An Update From the Society of Critical Care Medicine Tele-ICU Committee.

OBJECTIVES: In 2014, the Tele-ICU Committee of the Society of Critical Care Medicine published an article regarding the state of ICU telemedicine, one better defined today as tele-critical care. Given the rapid evolution in the field, the authors now provide an updated review. DATA SOURCES AND STUDY SELECTION: We searched PubMed and OVID for peer-reviewed literature published between 2010 and 2018 related to significant developments in tele-critical care, including its prevalence, function, activity, and technologies. Search terms included electronic ICU, tele-ICU, critical care telemedicine, and ICU telemedicine with appropriate descriptors relevant to each sub-section. Additionally, information from surveys done by the Society of Critical Care Medicine was included given the relevance to the discussion and was referenced accordingly. DATA EXTRACTION AND DATA SYNTHESIS: Tele-critical care continues to evolve in multiple domains, including organizational structure, technologies, expanded-use case scenarios, and novel applications. Insights have been gained in economic impact and human and organizational factors affecting tele-critical care delivery. Legislation and credentialing continue to significantly influence the pace of tele-critical care growth and adoption. CONCLUSIONS: Tele-critical care is an established mechanism to leverage critical care expertise to ICUs and beyond, but systematic research comparing different models, approaches, and technologies is still needed.

Access to internet, smartphone usage, and acceptability of mobile health technology among cancer patients.

PURPOSE: The use of mobile health (mHealth) technologies to augment patient care enables providers to communicate remotely with patients enhancing the quality of care and patient engagement. Few studies evaluated predictive factors of its acceptance and subsequent implementation, especially in medically underserved populations. METHODS: A cross-sectional study of 151 cancer patients was conducted at an academic medical center in the USA. A trained interviewer performed structured interviews regarding the barriers and facilitators of patients' current and desired use of mHealth technology for healthcare services. RESULTS: Of the 151 participants, 35.8% were male and ages ranged from 21 to 104 years. 73.5% of participants currently have daily access to internet, and 68.2% currently own a smartphone capable of displaying mobile applications. Among all participants, acceptability of a daily mHealth application was significantly higher in patients with a college-level degree (OR 2.78, CI95% 1.25-5.88) and lower in patients > 80 years of age (OR 0.05, CI95% 0.01-0.23). Differences in acceptability when adjusted for current smartphone use and daily access to internet were nonsignificant. Among smartphone users, the desire to increase cancer knowledge was associated with a higher likelihood of utilizing a mHealth application (OR 261.53, CI95% 10.13-6748.71). CONCLUSION: The study suggests that factors such as age, educational achievement, and access to internet are significant predictors of acceptability of a mHealth application among cancer patients. Healthcare organizations should consider these factors when launching patient engagement platforms.

The Effect of Sedation on Long-Term Psychological Impairment After Extracorporeal Life Support.

OBJECTIVE: This retrospective study aimed to identify the association between long-term psychological impairment and total sedation received during venovenous extracorporeal life support (VV-ECLS) for acute respiratory failure (ARF). DESIGN: This observational retrospective study compared characteristics between patients with and without long-term psychological morbidity at long-term follow-up after VV-ECLS for ARF. SETTING: A single institutional experience in a quaternary referral academic medical center in the United States. PATIENTS: Patients who received VV-ECLS for ARF between January 1, 2015, and April 1, 2017, were identified for selection. Presence of psychiatric morbidity (anxiety and/or depression) was determined with the Hospital Anxiety and Depression Subscale battery at long-term follow-up. INTERVENTIONS: No interventions were made during this retrospective observational study. MEASUREMENTS AND MAIN RESULTS: A total of 42 patients (21 male, 21 female, median age 49 [interquartile range {IQR} 36-57]) completed a telephone interview a median of 14.6 (IQR 7.7-21.1) months after ECLS decannulation. Cohorts were defined as possessing any psychiatric morbidity (anxiety and/or depression) as defined by the Hospital Anxiety and Depression Subscale battery (n = 22 [52%]) versus no psychiatric morbidity (n = 20 [48%]) at long-term follow-up. Patients who had clinically significant psychiatric morbidity received a median of 15.0 (IQR 11.0-17.0) days of continuous intravenous sedation compared with patients who had no psychiatric morbidity, who received a median of 10.0 (IQR 6.5-13.5) days of intravenous sedation; (p = 0.02). CONCLUSIONS: This retrospective analysis identified a significant association between the presence of long-term post-VV-ECLS psychiatric symptoms and the total number of days of intravenous sedation.

Narrative Review of Decision-Making Processes in Critical Care.

Several theories describing the decision-making process in the intensive care unit (ICU) have been formulated. However, none of them appreciate the complexities of the process in an eclectic way by unifying several miscellaneous variables in 1 comprehensive theory. The purpose of this review is to highlight the key intricacies associated with the decision-making process in the ICU, to describe the theoretical frameworks with a special emphasis on gaps of knowledge, and to offer some avenues for improvement. The application of theoretical framework helps us to understand and to modify the structure of the process. Expected utility theory, regret theory, prospect theory, fuzzy-trace theory, construal level theory, and quantum probability theory were formulated over the years to appreciate an increased complexity of the decision-making process in the ICU. However the decision makers engage, these models may affect patient care because each of these frameworks has several benefits and downsides. There are gaps of knowledge in understanding how physicians match the different theoretical frameworks of the decision-making process with the potentially high ICU variability and load, especially when the "best outcome" is often nondiscrete and multidimensional. Furthermore, it is unclear when the preferential application of reflexive, habitual, variable, and biased-prone processes results in patient and staff detriment. We suggest better matching of theoretical frameworks with strengths of the human decision-making process and balanced application computer aids, artificial intelligence, and organizational modifications. The key component of this integration is work to increase the self-awareness of decision-making processes among residents, fellows, and attending physicians.

Acute Respiratory Failure Managed via Inter-Facility Transport for Extracorporeal Life Support: A 3-Year Experience.

OBJECTIVES: The objectives of this study were as follows: (1) to describe a successful design for a mobile lung rescue program, focusing on challenges and resources required to support such a program, and (2) report short-term outcomes for patients placed on venovenous extracorporeal life support (VV-ECLS) by a transferring team before inter-facility transport to a specialized extracorporeal life support (ECLS) center. DESIGN: This retrospective review and analysis used patient chart review to collect outcomes data and resource demand. SETTING: A single institutional experience in an academic center in the United States. PARTICIPANTS: Patient selection targeted the 75 patients who were placed on VV-ECLS for acute respiratory failure at an outside institution by the authors' team before transport from January 1, 2015, through December 31, 2017. INTERVENTIONS: No intervention was made. MEASUREMENTS AND MAIN RESULTS: Average time for dispatch and transfer was 4 hours and 10 minutes for ground and 3 hours and 30 minutes for air transport (p = 0.029). Demand was highest in winter, with 61% (46/75) of patients presenting from November through April, and daytime, with 73% (55/75) occurring from 8 am to 8 pm. Demand increased during the study period, with 21 patients in 2015, 24 in 2016, and 30 in 2017. Mortality was low, with 72% of patients surviving to discharge. CONCLUSIONS: Herein a successful mobile lung rescue program for transfer to a regional ECLS center is described. These findings demonstrate bed availability during high census and presence of a physician for duration of transport. These challenges can be overcome and successful implementation can be made with low mortality, supporting the development of regional ECLS centers.

Use of veno-venous extracorporeal membrane oxygenation to treat severe combined calcium channel blocker and angiotensin converting enzyme inhibitor overdose.

INTRODUCTION: Calcium channel blockers (CCBs) are a commonly prescribed medication that, at toxic levels, are capable of causing severe refractory hypotension, hypoxic respiratory failure and cardiotoxicity. There is little evidence currently guiding the approach to managing CCB overdose, particularly when combined with other antihypertensive agents. CASE REPORT: We describe the use of veno-venous extracorporeal membrane oxygenation (VV ECMO) in a previously healthy man following combined overdose with amlodipine and lisinopril in a suicide attempt. ECMO was used to provide oxygenation support, allowing for the amlodipine and lisinopril to be metabolized and cleared while also reducing ventilator-induced lung injury (VILI) and avoiding the complications associated with venous-arterial (VA) ECMO, such as differential hypoxemia. CONCLUSION: Limited case reports suggesting the use of ECMO in CCB overdose have employed VA ECMO due to CCB-induced cardiotoxicity. We believe that, if cardiac function has been preserved, VV ECMO should be considered a viable treatment strategy for CCB and ACE-I overdose resulting in refractory hypoxemic respiratory failure.

Acquired immunological imbalance after surgery with cardiopulmonary bypass due to epigenetic over-activation of PU.1/M-CSF.

BACKGROUND: It has been shown that severe insult to the immune system may trigger prolonged macrophage characteristics associated with excessive release of monocyte colony stimulating factor (M-CSF). However, it is unclear how persistent is the macrophage-like characteristics in circulating monocytes (MO). In this study, 20 patients who underwent non-emergent cardiopulmonary bypass had their monocytes characterized before surgery and 3 months after surgery. METHODS: We assessed the macrophage characteristics of MO using cytokine production, surface marker expression, an ability to stimulate T cells, and methylation of the promoter region of the gene encoding PU.1, a critical component to M-CSF production. MO function as well as activation and differentiation potential were longitudinally assessed. RESULTS: At 3 months after cardiopulmonary bypass, monocytes exhibited increased expression of MRP8, transforming growth factor-ß/latency-associated peptide, suppressor of cytokine signaling 3 while phagocytic properties were increased. Concomitantly, we observed a decreased expression of CD86, a decreased ability to form regulatory dendritic cells, and a diminished ability to stimulate T cells. These characteristics were accompanied by a persistent increase in the secretion of M-CSF, over-activation of PU.1, and decreased methylation of the PU.1 promoter region. Serum levels of C-reactive protein and anti-cytomegalovirus IgG antibody titers were also elevated in some patients at 3 months after surgery. CONCLUSIONS: We concluded that at 3 months after cardiopulmonary bypass, monocytes continued to express a new macrophage-like milieu that was associated with the persistent activation of the PU.1/M-CSF pathway.

Content analysis of locum tenens recruitment emails for anesthesiologists.

BACKGROUND: Locum tenens continues to be an increasingly utilized employment option among healthcare organizations to cope with short-term provider vacancies. There exist no studies that explore the job characteristics of such assignments. The purpose of this study was to characterize the clinical responsibilities and compensation of anesthesiology locum tenens positions through content analysis of recruitment emails. Through this data, anesthesiologists interested in locum tenens will be better equipped to evaluate the merit of potential opportunities. METHODS: The study was conducted using a compiled database of unsolicited emails received by one of the authors. A total of 241 emails containing 794 assignments were included during the period of 1/09/17 to 1/26/18 (383 days in total). The information was extracted using a standardized template and was entered into a database. Additional validation of the content was done using a data mining tool. RESULTS: Most of the job opportunities originated from five staffing agencies. A total of 37, 25, and 17% of the assignments were allocated to hospitals, ambulatory surgical centers, and trauma centers respectively. The mean caseload for the assignments was between 8.5 and 11.1 cases per day. The mean daily work shift was 9.1 hours, and the average duration of the assignment was one week. The most frequently requested cases included general (74%), orthopedics (54%), and OB/GYN (51%). However, information regarding training qualifications and licensing was not routinely provided. Only 13.1% of assignments specified a system of medical documentation with paper charting being the most common. The mean hourly rate for locum anesthesiologists in our sample was $186.19, significantly higher than the national average of $127.88. Around 28% of staffing agencies covered the licensing expenses of specialists while 23% covered the expense of travels and 20% covered accommodation costs. CONCLUSIONS: Descriptions for locum tenens positions follow common anesthesiology practices and feature superior compensation to national estimates. However, vital information is often omitted from recruitment emails, and practice settings are highly variable. Anesthesiologists are urged to fully investigate opportunities before accepting based on recruitment emails. Managers should require more details to be provided in job offers.