Predicting Organ Dysfunction in Septic and Critically Ill Patients: A Prospective Cohort Study Using Rapid Ex Vivo Immune Profiling.

OBJECTIVES: While cytokine response patterns are pivotal in mediating immune responses, they are also often dysregulated in sepsis and critical illness. We hypothesized that these immunological deficits, quantifiable through ex vivo whole blood stimulation assays, may be indicative of subsequent organ dysfunction. DESIGN: In a prospective observational study, adult septic patients and critically ill but nonseptic controls were identified within 48 hours of critical illness onset. Using a rapid, ex vivo assay based on responses to lipopolysaccharide (LPS), anti-CD3/anti-CD28 antibodies, and phorbol 12-myristate 13-acetate with ionomycin, cytokine responses to immune stimulants were quantified. The primary outcome was the relationship between early cytokine production and subsequent organ dysfunction, as measured by the Sequential Organ Failure Assessment score on day 3 of illness (SOFAd3). SETTING: Patients were recruited in an academic medical center and data processing and analysis were done in an academic laboratory setting. PATIENTS: Ninety-six adult septic and critically ill nonseptic patients were enrolled. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Elevated levels of tumor necrosis factor and interleukin-6 post-endotoxin challenge were inversely correlated with SOFAd3. Interferon-gamma production per lymphocyte was inversely related to organ dysfunction at day 3 and differed between septic and nonseptic patients. Clustering analysis revealed two distinct immune phenotypes, represented by differential responses to 18 hours of LPS stimulation and 4 hours of anti-CD3/anti-CD28 stimulation. CONCLUSIONS: Our rapid immune profiling technique offers a promising tool for early prediction and management of organ dysfunction in critically ill patients. This information could be pivotal for early intervention and for preventing irreversible organ damage during the acute phase of critical illness.

Macrophage-derived human resistin promotes perivascular adipose tissue dysfunction in experimental inflammatory arthritis.

Cardiovascular disease (CVD) is the leading cause of death in rheumatoid arthritis (RA). Resistin is an adipokine that induces adipose tissue inflammation and activation of monocytes/macrophages via adenylate cyclase-associated protein-1 (CAP1). Resistin levels are increased in RA and might cause perivascular adipose tissue (PVAT) dysfunction, leading to vascular damage and CVD. This study aimed to investigate the role of resistin in promoting PVAT dysfunction by increasing local macrophage and inflammatory cytokines content in antigen-induced arthritis (AIA). Resistin pharmacological effects were assessed by using C57Bl/6J wild-type (WT) mice, humanized resistin mice expressing human resistin in monocytes-macrophages (hRTN+/-/-), and resistin knockout mice (RTN-/-) with AIA and respective controls. We investigated AIA disease activity and functional, cellular, and molecular parameters of the PVAT. Resistin did not contribute to AIA disease activity and its concentrations were augmented in the PVAT and plasma of WT AIA and hRTN+/-/- AIA animals. In vitro exposure of murine arteries to resistin impaired vascular function by decreasing the anti-contractile effect of PVAT. WT AIA mice and hRTN+/-/- AIA mice exhibited PVAT dysfunction and knockdown of resistin prevented it. Macrophage-derived cytokines, markers of types 1 and 2 macrophages, and CAP1 expression were increased in the PVAT of resistin humanized mice with AIA, but not in knockout mice for resistin. This study reveals that macrophage-derived resistin promotes PVAT inflammation and dysfunction regardless of AIA disease activity. Resistin might represent a translational target to reduce RA-driven vascular dysfunction and CVD.

Ex Vivo Endotoxin Stimulation of Blood for Predicting Survival in Patients With Sepsis: A Systematic Review.

BACKGROUND: Sepsis is a syndrome characterized by host immune dysfunction, with the extent of immunoparalysis differing among patients. Lipopolysaccharide (LPS) is used commonly to assess the immune function of critically ill patients with sepsis. However, the reliability of this ex vivo diagnostic test in predicting clinical outcomes remains uncertain. RESEARCH QUESTION: Does LPS-induced tumor necrosis factor (TNF) production from the blood of patients with sepsis predict mortality? Secondary outcomes included ICU and hospital stay durations, nosocomial infection rate, and organ recovery rate. STUDY DESIGN AND METHODS: Human sepsis studies from various databases through April 2023 were evaluated. Inclusion criteria encompassed LPS-stimulated blood assays, English language, and reported clinical outcomes. Bias risk was evaluated using the Newcastle-Ottawa scale (NOS). Relationships between TNF production and mortality were analyzed at sepsis onset and during established sepsis, alongside secondary outcomes. RESULTS: Of 11,580 studies, 17 studies (14 adult and three pediatric) were selected for analysis. Although 15 studies were evaluated as moderate to high quality using the NOS, it is important to note that some of these studies also had identifiable biases, such as unclear methods of participant recruitment. Nine studies detailed survival outcomes associated with LPS-induced TNF production at sepsis onset, whereas five studies explored TNF production's relationship with mortality during established sepsis. Trends suggested that lower LPS-induced TNF production correlated with higher mortality. However, heterogeneity in methodologies, especially the LPS assay protocol, hindered definitive conclusions. Publication bias was highlighted using funnel plot analysis. Concerning secondary outcomes, diminished TNF production might signify worsening organ dysfunction, although the link between cytokine production and nosocomial infection varied among studies. INTERPRETATION: For functional immune profiling in sepsis, streamlined research methodologies are essential. This entails organizing cohorts based on microbial sources of sepsis, establishing standardized definitions of immunoparalysis, using consistent types and dosages of immune stimulants, adhering to uniform blood incubation conditions, and adopting consistent clinical outcomes.

Gut microbiome dynamics and associations with mortality in critically ill patients.

BACKGROUND: Critical illness and care within the intensive care unit (ICU) leads to profound changes in the composition of the gut microbiome. The impact of such changes on the patients and their subsequent disease course remains uncertain. We hypothesized that specific changes in the gut microbiome would be more harmful than others, leading to increased mortality in critically ill patients. METHODS: This was a prospective cohort study of critically ill adults in the ICU. We obtained rectal swabs from 52 patients and assessed the composition the gut microbiome using 16 S rRNA gene sequencing. We followed patients throughout their ICU course and evaluated their mortality rate at 28 days following admission to the ICU. We used selbal, a machine learning method, to identify the balance of microbial taxa most closely associated with 28-day mortality. RESULTS: We found that a proportional ratio of four taxa could be used to distinguish patients with a higher risk of mortality from patients with a lower risk of mortality (p = .02). We named this binarized ratio our microbiome mortality index (MMI). Patients with a high MMI had a higher 28-day mortality compared to those with a low MMI (hazard ratio, 2.2, 95% confidence interval 1.1-4.3), and remained significant after adjustment for other ICU mortality predictors, including the presence of the acute respiratory distress syndrome (ARDS) and the Acute Physiology and Chronic Health Evaluation (APACHE II) score (hazard ratio, 2.5, 95% confidence interval 1.4-4.7). High mortality was driven by taxa from the Anaerococcus (genus) and Enterobacteriaceae (family), while lower mortality was driven by Parasutterella and Campylobacter (genera). CONCLUSIONS: Dysbiosis in the gut of critically ill patients is an independent risk factor for increased mortality at 28 days after adjustment for clinically significant confounders. Gut dysbiosis may represent a potential therapeutic target for future ICU interventions.

Pro-Con Debate: Should Critically Ill Patients Undergo Procedures at Bedside or in the Operating Room?

Nonoperating room anesthesia (NORA) is a fast-growing field in anesthesiology, wherein anesthesia care is provided for surgical procedures performed outside the main operating room (OR) pavilion. Advances in medical science and technology have led to an increasing number of procedures being moved out of the operating room to procedural suites. One such NORA location is the intensive care unit (ICU), where a growing number of urgent and emergent procedures are being performed on medically unstable patients. ICU-NORA allows medical care to be provided to patients who are too sick to tolerate transport between the ICU and the OR. However, offering the same, high-quality, and safe care in this setting may be challenging. It requires special planning and a thorough consideration of the presence of life-threatening comorbidities and location-specific and ergonomic barriers. In this Pro-Con commentary article, we discuss these special considerations and argue in favor of and against routinely performing procedures at the bedside in the ICU versus in the OR.

Comparison of whole blood cytokine immunoassays for rapid, functional immune phenotyping in critically ill patients with sepsis.

BACKGROUND: Sepsis is characterized by highly heterogeneous immune responses associated with a spectrum of disease severity. Methods that rapidly and sensitively profile these immune responses can potentially personalize immune-adjuvant therapies for sepsis. We hypothesized that the ELLA microfluidic approach to measure cytokine production from the whole blood of septic and critically ill patients would deliver faster, more precise results than the existing optic-driven ELISpot quantification. We tested our hypothesis by measuring ex vivo-stimulated production of TNF and IFNγ in critically ill and septic patients (n = 22), critically ill and non-septic patients (n = 10), and healthy volunteers (n = 10) through both ELLA and ELISpot immunoassays. Blood samples were subjected to one of three stimulants for 4 h or 18 h durations during days 1, 7-10, and 14 of critical illness. Stimulants for lymphocytes included anti-CD3/anti-CD28 and phorbol 12-myristate 13-acetate (PMA), whereas LPS was used for monocytes. Stimulated TNF and IFNγ concentrations were then associated with 30-day mortality. RESULTS: Both ELISpot and ELLA immunoassays showed substantial agreement in TNF concentrations post 4 h and 18 h LPS stimulation, with concordance correlation coefficients at 0.62 and 0.60, respectively. ELLA had a broad dynamic measurement range and provided accurate TNF and IFNγ readings at both minimal and elevated cytokine concentrations (with mean coefficients of variation between triplicate readings at 2.1 ± 1.4% and 4.9 ± 7.2%, respectively). However, there was no association between the ELLA-determined cytokine concentrations on the first day of critical illness and 30-day mortality rate. In contrast, using the ELISpot for cytokine quantification revealed that non-survivors had reduced baseline TNF levels at 18 h, decreased LPS-induced TNF levels at 18 h, and diminished TNF levels post 4 h/18 h anti-CD3/28 stimulation. CONCLUSIONS: Our study affirms the feasibility of obtaining dependable immune phenotyping data within 6 h of blood collection from critically ill patients, both septic and non-septic, using the ELLA immunoassay. Both ELLA and ELISpot can offer valuable insights into prognosis, therapeutic strategies, and the underlying mechanisms of sepsis development.

Long-term clinical outcomes in critically ill patients with sepsis and pre-existing low muscle mass: a retrospective cohort study.

PURPOSE: Critically ill patients with sepsis account for significant disease morbidity and healthcare costs. Low muscle mass has been proposed as an independent risk factor for poor short-term outcomes, although its effect on long-term outcomes remains unclear. METHODS: Retrospective cohort analysis of patients treated at a quaternary care medical center over 6 years (09/2014 - 12/2020). Critically ill patients meeting Sepsis-3 criteria were included, with low muscle mass defined by [Formula: see text] 5th percentile skeletal muscle index, measured at the L3 lumbar level (L3SMI) on Computed-Tomography (CT) scan ([Formula: see text] 41.6 cm2/m2 for males and [Formula: see text] 32.0 cm2/m2 for females). L3SMI was calculated by normalizing the CT-measured skeletal muscle area to the square of the patient's height (in meters). Measurements were taken from abdominal/pelvic CT scan obtained within 7 days of sepsis onset. The prevalence of low muscle mass and its association with clinical outcomes, including in-hospital and one-year mortality, and post-hospitalization discharge disposition in survivors, was analyzed. Unfavorable post-hospitalization disposition was defined as discharge to a location other than the patient's home. RESULTS: Low muscle mass was present in 34 (23%) of 150 patients, with mean skeletal muscle indices of 28.0 ± 2.9 cm2/m2 and 36.8 ± 3.3 cm2/m2 in females and males, respectively. While low muscle mass was not a significant risk factor for in-hospital mortality (hazard ratio 1.33; 95% CI 0.64 - 2.76; p = 0.437), it significantly increased one-year mortality after adjusting for age and illness severity using Cox multivariate regression (hazard ratio 1.9; 95% CI 1.1 - 3.2; p = 0.014). Unfavorable post-hospitalization discharge disposition was not associated with low muscle mass, after adjusting for age and illness severity in a single, multivariate model. CONCLUSION: Low muscle mass independently predicts one-year mortality but is not associated with in-hospital mortality or unfavorable hospital discharge disposition in critically ill patients with sepsis.

Comparing Long-Term Prognosis in Chronic Critically Ill Patients: A Case Series Study of Medical versus Surgical Sepsis.

Background and Objectives: Chronic critical illness (CCI) is a syndrome characterized by persistent organ dysfunction that requires critical care therapy for ≥14 days. Sepsis and respiratory failure constitute the two primary causes of CCI. A better understanding of this patient population and their clinical course may help to risk-stratify them early during hospitalization. Our objective was to identify whether the source of sepsis (medical versus surgical) affected clinical trajectory and prognosis in patients developing CCI. Materials and Methods: We describe a cohort of patients having acute respiratory failure and sepsis and requiring critical care therapy in the medical (MICU) or surgical (SICU) critical care units for ≥14 days. Given the relative infrequency of CCI, we use a case series design to examine mortality, functional status, and place of residence (home versus non-home) at one year following their index hospitalization. Results: In medical patients developing CCI (n = 31), the severity of initial organ dysfunction, by SOFA score, was significantly associated with the development of CCI (p = 0.002). Surgical patients with CCI (n = 7) experienced significantly more ventilator-free days within the first 30 days following sepsis onset (p = 0.004), as well as less organ dysfunction at day 14 post-sepsis (p < 0.0001). However, one-year mortality, one-year functional status, and residency at home were not statistically different between cohorts. Moreover, 57% of surgical patients and 26% of medical patients who developed CCI were living at home for one year following their index hospitalization (p = 0.11). Conclusions: While surgical patients who develop sepsis-related CCI experience more favorable 30-day outcomes as compared with medical patients, long-term outcomes do not differ significantly between groups. This suggests that reversing established organ dysfunction and functional disability, regardless of etiology, is more challenging compared to preventing these complications at an earlier stage.

Emergency use of sugammadex after failure of standard reversal drugs and postoperative pulmonary complications: A retrospective cohort study.

Background and Aims: The use of sugammadex instead of neostigmine for the reversal of neuromuscular blockade may decrease postoperative pulmonary complications. It is unclear if this finding is applicable to situations where sugammadex is administered after the administration of neostigmine. The objective of this study was to compare the incidence of a composite outcome measure of major postoperative pulmonary complications in patients who received sugammadex as a rescue agent after neostigmine versus those who received sugammadex alone for reversal of neuromuscular blockade. Material and Methods: This retrospective cohort study analyzed the medical records of adult patients who underwent elective inpatient noncardiac surgery under general anesthesia and received sugammadex for reversal of neuromuscular blockade, at a tertiary care academic hospital between August 2016 and November 2018. Results: A total of 1,672 patients were included, of whom 1,452 underwent reversal with sugammadex alone and 220 received sugammadex following reversal with neostigmine/glycopyrrolate. The composite primary outcome was diagnosed in 60 (3.6%) patients. Comparing these two groups, and after adjusting for confounding factors, patients who received sugammadex after reversal with neostigmine had more postoperative pulmonary complications than those reversed with sugammadex alone (6.8% vs. 3.1%, odds ratio, 2.29; 95% confidence interval [CI], 1.25 to 4.18; P = 0.006). Conclusion: The use of sugammadex following reversal with neostigmine was associated with a higher incidence of postoperative pulmonary complications as compared to the use of sugammadex alone. The implications of using sugammadex after the failure of standard reversal drugs should be investigated in prospective studies.

Mesenchymal stromal cells and alpha-1 antitrypsin have a strong synergy in modulating inflammation and its resolution.

Rationale: Trauma, surgery, and infection can cause severe inflammation. Both dysregulated inflammation intensity and duration can lead to significant tissue injuries, organ dysfunction, mortality, and morbidity. Anti-inflammatory drugs such as steroids and immunosuppressants can dampen inflammation intensity, but they derail inflammation resolution, compromise normal immunity, and have significant adverse effects. The natural inflammation regulator mesenchymal stromal cells (MSCs) have high therapeutic potential because of their unique capabilities to mitigate inflammation intensity, enhance normal immunity, and accelerate inflammation resolution and tissue healing. Furthermore, clinical studies have shown that MSCs are safe and effective. However, they are not potent enough, alone, to completely resolve severe inflammation and injuries. One approach to boost the potency of MSCs is to combine them with synergistic agents. We hypothesized that alpha-1 antitrypsin (A1AT), a plasma protein used clinically and has an excellent safety profile, was a promising candidate for synergism. Methods: This investigation examined the efficacy and synergy of MSCs and A1AT to mitigate inflammation and promote resolution, using in vitro inflammatory assay and in vivo mouse acute lung injury model. The in vitro assay measured cytokine releases, inflammatory pathways, reactive oxygen species (ROS), and neutrophil extracellular traps (NETs) production by neutrophils and phagocytosis in different immune cell lines. The in vivo model monitored inflammation resolution, tissue healing, and animal survival. Results: We found that the combination of MSCs and A1AT was much more effective than each component alone in i) modulating cytokine releases and inflammatory pathways, ii) inhibiting ROS and NETs production by neutrophils, iii) enhancing phagocytosis and, iv) promoting inflammation resolution, tissue healing, and animal survival. Conclusion: These results support the combined use of MSCs, and A1AT is a promising approach for managing severe, acute inflammation.

Long-Term Clinical Outcomes in Critically Ill Patients with Sepsis and Pre-existing Sarcopenia: A Retrospective Cohort Study.

Purpose: Critically ill patients with sepsis account for significant disease morbidity and healthcare costs. Sarcopenia has been proposed as an independent risk factor for poor short-term outcomes, although its effect on long-term outcomes remains unclear. Methods: Retrospective cohort analysis of patients treated at a tertiary care medical center over 6 years (09/2014 - 12/2020). Critically ill patients meeting Sepsis-3 criteria were included, with sarcopenia defined by skeletal muscle index at the L3 lumbar area on abdominal Computed-Tomography scan. The prevalence of sarcopenia and its association with clinical outcomes was analyzed. Results: Sarcopenia was present in 34 (23%) of 150 patients, with median skeletal muscle indices of 28.1 cm 2 /m 2 and 37.3 cm 2 /m 2 in sarcopenic females and males, respectively. In-hospital mortality was not associated with sarcopenia when adjusted for age and illness severity. One year mortality was increased in sarcopenic patients, after adjustment for illness severity (HR 1.9, p = 0.02) and age (HR 2.4, p = 0.001). However, it was not associated with increased likelihood for discharge to long-term rehabilitation or hospice care in adjusted analyses. Conclusion: Sarcopenia independently predicts one year mortality but is not associated with unfavorable hospital discharge disposition in critically ill patients with sepsis.

Integrated machine learning approaches for flow cytometric quantification of myeloid-derived suppressor cells in acute sepsis.

Highly heterogeneous cell populations require multiple flow cytometric markers for appropriate phenotypic characterization. This exponentially increases the complexity of 2D scatter plot analyses and exacerbates human errors due to variations in manual gating of flow data. We describe a semi-automated workflow, based entirely on the Flowjo Graphical User Interface (GUI), that involves the stepwise integration of several, newly available machine learning tools for the analysis of myeloid-derived suppressor cells (MDSCs) in septic and non-septic critical illness. Supervised clustering of flow cytometric data showed correlation with, but significantly different numbers of, MDSCs as compared with the cell numbers obtained by manual gating. Neither quantification method predicted 30-day clinical outcomes in a cohort of 16 critically ill and septic patients and 5 critically ill and non-septic patients. Machine learning identified a significant decrease in the proportion of PMN-MDSC in critically ill and septic patients as compared with healthy controls. There was no difference between the proportion of these MDSCs in septic and non-septic critical illness.

Comparison of Rapid Cytokine Immunoassays for Functional Immune Phenotyping.

Background: Cell-based functional immune-assays may allow for risk stratification of patients with complex, heterogeneous immune disorders such as sepsis. Given the heterogeneity of patient responses and the uncertain immune pathogenesis of sepsis, these assays must first be defined and calibrated in the healthy population. Objective: Our objective was to compare the internal consistency and practicality of two immune assays that may provide data on surrogate markers of the innate and adaptive immune response. We hypothesized that a rapid turnaround, microfluidic-based immune assay (ELLA) would be comparable to a dual-color, enzyme-linked immunospot (ELISpot) assay in identifying tumor necrosis factor (TNF) and interferon (IFN)γ production following ex vivo whole blood stimulation. Design: This was a prospective, observational cohort analysis. Whole blood samples from ten healthy, immune-competent volunteers were stimulated for either 4 hours or 18 hours with lipopolysaccharide, anti-CD3/anti-CD28 antibodies, or phorbol 12-myristate 13-acetate with ionomycin to interrogate innate and adaptive immune responses, respectively. Measurements and Main Results: ELLA analysis produced more precise measurement of TNF and IFNγ concentrations as compared with ELISpot, as well as a four- to five-log10 dynamic range for TNF and IFNγ concentrations, as compared with a two-log10 dynamic range with ELISpot. Unsupervised clustering accurately predicted the ex vivo immune stimulant used for 90% of samples analyzed via ELLA, as compared with 72% of samples analyzed via ELISpot. Conclusions: We describe, for the first time, a rapid and precise assay for functional interrogation of the innate and adaptive arms of the immune system in healthy volunteers. The advantages of the ELLA microfluidic platform may represent a step forward in generating a point-of-care test with clinical utility, for identifying deranged immune phenotypes in septic patients.

Failure to Rescue After Severe Acute Kidney Injury in Patients Undergoing Non-Cardiac Surgery.

INTRODUCTION: Many deaths after surgery can be attributed to "failure to rescue," which may be a better surgical quality indicator than the occurrence of a postoperative complication. Acute kidney injury (AKI) is one such postoperative complication associated with high mortality. The purpose of this study is to identify perioperative risk factors associated with failure to rescue among patients who develop postoperative AKI. METHODS: We identified adult patients who underwent non-cardiac surgery between 2012 and 2018 and experienced postoperative severe AKI (an increase in blood creatinine concentration of >2 mg/dL above baseline or requiring hemodialysis) from the American College of Surgeons National Surgical Quality Improvement Program database. Multivariable logistic regression was used to identify risk factors for failure to rescue among patients who developed severe AKI. RESULTS: Among 5,765,904 patients who met inclusion criteria, 26,705 (0.46%) patients developed postoperative severe AKI, of which 6834 (25.6%) experienced failure to rescue. Risk factors with the strongest association (adjusted odds ratio >1.5) with failure to rescue in patients with AKI included advanced age, higher American Society of Anesthesiologists class, presence of preoperative ascites, disseminated cancer, septic shock, and blood transfusion within 72 h of surgery start time. CONCLUSIONS: About one-fourth of patients who develop severe AKI after non-cardiac surgery die within 30 d of surgery. Both patient- and surgery-related risk factors are associated with this failure to rescue. Further studies are needed to identify early and effective interventions in high-risk patients who develop postoperative severe AKI to prevent the antecedent mortality.

Resistin production does not affect outcomes in a mouse model of acute surgical sepsis.

INTRODUCTION: Because of the strong correlation between the blood concentration of circulating resistin and the illness severity of septic patients, resistin has been proposed as a mediator of sepsis pathophysiology. In vitro data indicate that human resistin directly impairs neutrophil migration and intracellular bacterial killing, although the significance of these findings in vivo remain unclear. OBJECTIVE: The objectives of the present study were: (1) to validate the expression of human resistin in a clinically relevant, murine model of surgical sepsis, (2) to assess how sepsis-induced changes in resistin correlate with markers of infection and organ dysfunction, and (3) to investigate whether the expression of human resistin alters immune function or disease outcomes in vivo. METHODS: 107 male, C57BL/6 mice transgenic for the human resistin gene and its promoter elements (Retn+/-/-, or Retn+) were generated on a Retn-/- (mouse resistin knockout, or Rko) background. Outcomes were compared between age-matched transgenic and knockout mice. Acute sepsis was defined as the initial 24 h following cecal ligation and puncture (CLP). Physiologic and laboratory parameters correlating to the human Sequential Organ Failure Assessment (SOFA) Score were measured in mice, and innate immune cell number/function in the blood and peritoneal cavity were assessed. RESULTS: CLP significantly increased circulating levels of human resistin. The severity of sepsis-induced leukopenia was comparable between Retn+ and Rko mice. Resistin was associated with increased production of neutrophil reactive oxygen species, a decrease in circulating neutrophils at 6 h and an increase in peritoneal Ly6Chi monocytes at 6 h and 24 h post-sepsis. However, intraperitoneal bacterial growth, organ dysfunction and mouse survival did not differ with resistin production in septic mice. SIGNIFICANCE: Ex vivo resistin-induced impairment of neutrophil function do not appear to translate to increased sepsis severity or poorer outcomes in vivo following CLP.

Renohepatic crosstalk: a review of the effects of acute kidney injury on the liver.

Several theories regarding acute kidney injury (AKI)-related mortality have been entertained, although mounting evidence supports the paradigm that impaired kidney function directly and adversely affects the function of several remote organs. The kidneys and liver are fundamental to human metabolism and detoxification, and it is therefore hardly surprising that critical illness complicated by hepatorenal dysfunction portends a poor prognosis. Several diseases can simultaneously impact the proper functioning of the liver and kidneys, although this review will address the impact of AKI on liver function. While evidence for this relationship in humans remains sparse, we present supportive studies and then discuss the most likely mechanisms by which AKI can cause liver dysfunction. These include 'traditional' complications of AKI (uremia, volume overload and acute metabolic acidosis, among others) as well as systemic inflammation, hepatic leukocyte infiltration, cytokine-mediated liver injury and hepatic oxidative stress. We conclude by addressing the therapeutic implications of these findings to clinical medicine.

Prerenal acute kidney injury-still a relevant term in modern clinical practice?

The traditional taxonomy of acute kidney injury (AKI) has remained pervasive in clinical nephrology. While the terms 'prerenal', 'intrarenal' and 'postrenal' highlight the diverse pathophysiology underlying AKI, they also imply discrete disease pathways and de-emphasize the nature of AKI as an evolving clinical syndrome with multiple, often simultaneous and overlapping, causes. In a similar vein, prerenal AKI comprises a diverse spectrum of kidney disorders, albeit one that is often managed by using a standardized clinical algorithm. We contend that the term 'prerenal' is too vague to adequately convey our current understanding of hypoperfusion-related AKI and that it should thus be avoided in the clinical setting. Practice patterns among nephrologists indicate that AKI-related terminology plays a significant role in the approaches that clinicians take to patients that have this complex disease. Thus, it appears that precise terminology does impact the treatment that patients receive. We will outline differences in the diagnosis and management of clinical conditions lying on the so-called prerenal disease spectrum to advocate caution when administering intravenous fluids to these clinically decompensated patients. An understanding of the underlying pathophysiology may, thus, avert clinical missteps such as fluid and vasopressor mismanagement in tenuous or critically ill patients.

Anesthetic Management and 30-Day Outcomes After Renal Autotransplantation.

Background: Renal autotransplantation is a complex procedure performed for various indications such as treatment of renal vascular and urologic lesions and loin pain hematuria syndrome (LPHS). Because of the rarity of the procedure, few reports have been published, and little is known about anesthetic management and postoperative outcomes of patients with LPHS. The goal of this study was to review and describe all cases of renal autotransplantation performed at Cleveland Clinic during a specified period, focusing on anesthetic management and postoperative 30-day outcomes. Methods: We performed a retrospective review of the records of all patients who underwent renal autotransplantation from 2005 to 2014 at the Cleveland Clinic and collected demographic, anesthetic, surgical, and postoperative data. Results: A total of 64 patients underwent renal autotransplantation from 2005 to 2014. The most frequent indications were nephrolithiasis and LPHS. General endotracheal anesthesia with epidural for pain control was used in 47% of cases. Median duration of anesthesia was 528 minutes. Most patients were sent to a regular nursing floor postoperatively, but 28% of patients required intensive care unit admission. Two patients developed graft ischemia, and 1 patient developed graft failure requiring nephrectomy. No anesthetic-related complications and no mortality were associated with this procedure during the study. Conclusion: Renal autotransplantation is a safe option for patients with LPHS. Additional studies are needed to assess the effect of intraoperative anesthetic management on outcomes in this patient population.

To Clot or Not: HELLP Syndrome and Disseminated Intravascular Coagulation in an Eclamptic Patient with Intrauterine Fetal Demise.

A 39-year-old G2P1001 female presented from an outside hospital following an eclamptic seizure in the setting of HELLP syndrome. This condition was complicated by intrauterine fetal demise and disseminated intravascular coagulation, which required an emergent cesarean section. We report the work-up and intraoperative and postoperative management of this complex patient with multiple medical needs. We focus on the hemostatic abnormalities in this patient and describe how our management would differ from that of a similar, nonpregnant patient.