Integrating New Staff into Endovascular Stroke-Treatment Workflows in the COVID-19 Pandemic.

A health care crisis such as the coronavirus disease 2019 (COVID-19) pandemic requires allocation of hospital staff and resources on short notice. Thus, new and sometimes less experienced team members might join the team to fill in the gaps. This scenario can be particularly challenging in endovascular stroke treatment, which is a highly specialized task that requires seamless cooperation of numerous health care workers across various specialties and professions. This document is intended for stroke teams who face the challenge of integrating new team members into endovascular stroke-treatment workflows during the COVID-19 pandemic or any other global health care emergency. It discusses the key strategies for smooth integration of new stroke-team members in a crisis situation: 1) transfer of key knowledge (simple take-home messages), 2) open communication and a nonjudgmental atmosphere, 3) strategic task assignment, and 4) graded learning and responsibility. While these 4 key principles should generally be followed in endovascular stroke treatment, they become even more important during health care emergencies such as the COVID-19 pandemic, when health care professionals have to take on new and additional roles and responsibilities in challenging working environments for which they were not specifically trained.

The efficacy of unilateral laparoscopic nephrectomy in the pediatric hypertensive patient.

BACKGROUND: Secondary hypertension due to a poorly functioning or non-functional kidney may be refractory to medical management. In such cases, nephrectomy can improve or cure hypertension. With the routine use of laparoscopy, nephrectomy can be performed in a minimally invasive manner, but surgery still carries inherent risks and complications. OBJECTIVE: The objective of this study is to evaluate the outcomes of laparoscopic nephrectomy performed for secondary hypertension and identify potential predictors of postoperative hypertension resolution. METHODS: After obtaining approval from institutional review board, patients from January 2002 to March 2018 who underwent laparoscopic nephrectomy were identified using Current Procedural Technology codes. All charts were then manually reviewed to isolate those patients with secondary hypertension present preoperatively. Patient demographics, urologic history, and laboratory and imaging findings were recorded for all patients. Serial blood pressures were recorded at all renal visits along with any antihypertensive medication changes. Postoperative outcomes and complications were also noted for all patients. RESULTS: A total of 20 patients (7 girls, 13 boys) underwent laparoscopic nephrectomy to treat hypertension at an average age of 10.6 years (range 1.7-17.0 years). Etiology of a solitary non-functional kidney was vesicoureteral reflux in 10 of 20 patients, multicystic dysplastic kidney in 5 of 20, ureteropelvic junction obstruction in 2 of 20, ureteral obstruction in 1 of 20, and renal artery stenosis in 2 of 20 patients. At time of surgery, 3 of 20 patients were on two antihypertensives, 10 of 20 were on one antihypertensive, and 7 of 20 proceeded to surgery with no medical management. In the 30-day postoperative period, no complications were noted. Hypertension improved in 10 of 20 (50%) patients, all of whom were not on any antihypertensive medications after surgery. Hypertension persisted in 4 of 20 (20%) patients, requiring the same antihypertensive regimen and worsened in 6 of 20 (30%) patients, requiring increased doses and/or additional antihypertensives. Average follow-up time was 2.7 years. No significant predictors of postoperative hypertension result were identified when comparing the groups of responders and non-responders. DISCUSSION: While laparoscopic nephrectomy for a non-functioning kidney in the setting of hypertension is a safe procedure, the cure rate for hypertension in the cohort appears to be on the low side of what was previously reported. While the small sample size is a main limitation, it is among the largest sample sizes for pediatric hypertensive patients. Previously shown predictors were not predictive in the similar-sized cohort. CONCLUSIONS: Patients should be carefully counseled on the risks and benefits of nephrectomy to treat hypertension, the importance of continued follow-up after nephrectomy, and the possible need for chronic medical management with antihypertensives.

Do pediatricians routinely perform genitourinary examinations during well-child visits? A review from a large tertiary pediatric hospital.

BACKGROUND: The male genital examination is a common source of discomfort for the patient and medical provider. Performance of male genital examination is imperative; however, as many treatable diagnoses can be made. Undescended testicles (UDTs), hernias, testicular tumors, and urethral abnormalities are all potentially concerning findings which can be discovered on routine examination. OBJECTIVE: The objectives of this study are to determine the rate at which general pediatricians perform routine genitourinary (GU) examinations in the pediatric population and to determine the rate at which UDT are diagnosed or documented in the patient's history. The authors hypothesize the rate of pediatric GU examination during routine well-child visits to be in line with the previously reported rates in the adult literature. STUDY DESIGN: Nine hundred ninety-six consecutive male well-child visits conducted by general pediatricians at the study institution were reviewed. These visits were evaluated for documentation of a detailed GU examination as well as the presence of UDT from these examinations. In addition, past medical and surgical histories were reviewed to determine if a diagnosis of UDT was noted. RESULTS: Pediatricians at the study institution documented GU examinations 99.1% of the time during male well-child visits. Only 1.1% of the cohort had a documentation of UDT at any time point. Of the 11 patients with UDT, 6 boys (54.5%) had spontaneous descent with no referral to urology, whereas 5 (45.5%) required orchidopexy. DISCUSSION: Prior reports suggest 70-75% of routine office visits include a genital examination. None of these reports reviewed the pediatric population, thus making this review novel in this respect. In addition, the results are vastly different from these prior studies as the authors demonstrated over 99% of male well-child examinations included documentation of a thorough genital examination. A limitation of the study is its retrospective nature, which creates a lack of standardization across the data set. In addition, without being physically present in the examination room, one cannot discern whether an examination is simply being documented without actual performance because of the template format of the electronic medical record (EMR). Furthermore, the study was not designed to best evaluate the true rate of UDTs; therefore, the reported rate of 1.1% cannot be accurately associated with a particular age at diagnosis. CONCLUSIONS: Pediatricians do, in fact, document GU examinations on a routine basis. This finding cannot be taken with complete certainty as verification of actual examination performance is impractical. While the data demonstrated a lower than expected rate of UDT, depending upon age at diagnosis, this could indicate that although examinations are being documented, their accuracy may be diminished because of various factors at play in the healthcare system as a whole, including improper exam performance and EMR templates. Follow-up studies are required to verify these potentially changing rates of UDT and to determine if there is discordance between documentation and performance of GU examinations.

Comparing treatment modalities for transplant kidney vesicoureteral reflux in the pediatric population.

INTRODUCTION: Non-refluxing ureteral reimplantation is favored in pediatric renal transplantation to prevent complications, such as vesicoureteral reflux (VUR) in the transplant ureter. VUR resulting in febrile urinary tract infections remains a problem in this population, leading to repeated hospitalizations and increased morbidity. Revision of the vesicoureteral anastomosis can be a surgical challenge due to scar tissue and tenuous vascularity of the transplant ureter. Therefore, alternative options such as endoscopic injection of Deflux at the neo-orifice and surveillance with prophylactic antibiotics have emerged as potential treatment modalities for transplant ureter VUR. OBJECTIVE: The authors reviewed their experience of the management of VUR in the transplant ureter, comparing outcomes of various modalities. STUDY DESIGN: With Institutional Review Board approval, a retrospective chart review of all renal transplant patients from January 2002 to January 2017 was conducted. All patients with VUR on voiding cystourethrogram (VCUG) after surgery were identified. Indications for end-stage renal disease, urologic comorbidities, pretransplant VCUG, and operative details were recorded. After transplantation, febrile urinary tract infections, ultrasound findings, and any further interventions-surveillance, subureteral endoscopic injection of Deflux, or ureteral reimplantation-were documented along with their outcomes. RESULTS: Overall, VUR was identified in 35/285 (12.3%) transplant patients after a non-refluxing ureteroneocystostomy. VUR was managed with surveillance in 17/35 (49%), intravesical Deflux injection in 11/35 (31%), and immediate redo ureteral reimplantation in 7/35 (20%). Ten out of 11 patients undergoing Deflux injection had a postoperative VCUG. All patients developed VUR recurrence; the majority showed immediate failure and only 1/10 showed late recurrence. Of the immediate failures, 3/9 patients were maintained on prophylactic antibiotics, and 6/9 patients underwent ureteral reimplantation. In these six patients undergoing reimplantation after failed Deflux, 3/6 (50%) patients required additional surgeries: One patient developed recurrence of reflux and two patients developed ureterovesical junction obstruction. In contrast, no complications were seen in patients undergoing primary ureteral reimplantation. DISCUSSION: The study is limited by low numbers and a retrospective design. However, the results of this study differ significantly from the published Deflux series showing a success rate of more than 50% in the treatment of transplant kidney VUR. In fact, post-Deflux redo ureteral reimplantation was associated with an increased risk of postoperative complication. CONCLUSION: The use of Deflux in the post-transplant setting has poor results. In the study series, 11/11 patients demonstrated clinical and radiographic failure. Therefore, as an institution the authors do not recommend Deflux as first-line treatment of VUR in the transplant patient.

Neurologic complications of cardiac and vascular surgery.

This chapter will provide an overview of the major neurologic complications of common cardiac and vascular surgeries, such as coronary artery bypass grafting and carotid endarterectomy. Neurologic complications after cardiac and vascular surgeries can cause significant morbidity and mortality, which can negate the beneficial effects of the intervention. Some of the complications to be discussed include ischemic and hemorrhagic stroke, seizures, delirium, cognitive dysfunction, cerebral hyperperfusion syndrome, cranial nerve injuries, and peripheral neuropathies. The severity of these complications can range from mild to lethal. The etiology of complications can include a variety of mechanisms, which can differ based on the type of cardiac or vascular surgery that is performed. Our knowledge about neuropathology, prevention, and management of surgical complications is growing and will be discussed in this chapter. It is imperative for clinicians to be familiar with these complications in order to narrow the differential diagnosis, start early management, anticipate the natural history, and improve outcomes.

Galaxies at redshifts 5 to 6 with systematically low dust content and high [C II] emission.

The rest-frame ultraviolet properties of galaxies during the first three billion years of cosmic time (redshift z > 4) indicate a rapid evolution in the dust obscuration of such galaxies. This evolution implies a change in the average properties of the interstellar medium, but the measurements are systematically uncertain owing to untested assumptions and the inability to detect heavily obscured regions of the galaxies. Previous attempts to measure the interstellar medium directly in normal galaxies at these redshifts have failed for a number of reasons, with two notable exceptions. Here we report measurements of the forbidden C ii emission (that is, [C II]) from gas, and the far-infrared emission from dust, in nine typical star-forming galaxies about one billion years after the Big Bang (z ≈ 5-6). We find that these galaxies have thermal emission that is less than 1/12 that of similar systems about two billion years later, and enhanced [C II] emission relative to the far-infrared continuum, confirming a strong evolution in the properties of the interstellar medium in the early Universe. The gas is distributed over scales of one to eight kiloparsecs, and shows diverse dynamics within the sample. These results are consistent with early galaxies having significantly less dust than typical galaxies seen at z < 3 and being comparable in dust content to local low-metallicity systems.

Efficacy and tolerability of pharmacotherapy options for the treatment of medullary thyroid cancer.

Metastatic and unresectable medullary thyroid carcinoma (MTC) is often difficult to treat as it is relatively unresponsive to radiation and conventional chemotherapy. This emphasizes the importance of the development of targeted therapies for advanced MTC. Vandetanib was approved by the US Food and Drug Administration for the treatment of symptomatic or progressive MTC in patients with advanced disease in April 2011. This therapy proved to be a breakthrough in the management of MTC. We review the efficacy and safety of this novel treatment and other treatments that are being evaluated in this disease.

Neurocritical care education during neurology residency: AAN survey of US program directors.

OBJECTIVE: Limited information is available regarding the current state of neurocritical care education for neurology residents. The goal of our survey was to assess the need and current state of neurocritical care training for neurology residents. METHODS: A survey instrument was developed and, with the support of the American Academy of Neurology, distributed to residency program directors of 132 accredited neurology programs in the United States in 2011. RESULTS: A response rate of 74% (98 of 132) was achieved. A dedicated neuroscience intensive care unit (neuro-ICU) existed in 64%. Fifty-six percent of residency programs offer a dedicated rotation in the neuro-ICU, lasting 4 weeks on average. Where available, the neuro-ICU rotation was required in the vast majority (91%) of programs. Neurology residents' exposure to the fundamental principles of neurocritical care was obtained through a variety of mechanisms. Of program directors, 37% indicated that residents would be interested in performing away rotations in a neuro-ICU. From 2005 to 2010, the number of programs sending at least one resident into a neuro-ICU fellowship increased from 14% to 35%. CONCLUSIONS: Despite the expansion of neurocritical care, large proportions of US neurology residents have limited exposure to a neuro-ICU and neurointensivists. Formal training in the principles of neurocritical care may be highly variable. The results of this survey suggest a charge to address the variability of resident education and to develop standardized curricula in neurocritical care for neurology residents.

The use of mouse models to investigate shear bond strength in amelogenesis imperfecta.

Patients with amelogenesis imperfecta (AI) have defective enamel; therefore, bonded restorations of patients with AI have variable success rates. To distinguish which cases of AI may have good clinical outcomes with bonded materials, we evaluated etching characteristics and bond strength of enamel in mouse models, comparing wild-type (WT) with those having mutations in amelogenin (Amelx) and matrix metalloproteinase-20 (Mmp20), which mimic 2 forms of human AI. Etched enamel surfaces were compared for roughness by scanning electron microscopy (SEM) images. Bonding was compared through shear bond strength (SBS) studies with 2 different systems (etch-and-rinse and self-etch). Etched enamel surfaces of incisors from Amelx knock-out (AmelxKO) mice appeared randomly organized and non-uniform compared with WT. Etching of Mmp20KO surfaces left little enamel, and the etching pattern was indistinguishable from unetched surfaces. SBS results were significantly different when AmelxKO and Mmp20KO enamel surfaces were compared. A significant increase in SBS was measured for all samples when the self-etch system was compared with the etch-and-rinse system. We have developed a novel system for testing shear bond strength of mouse incisors with AI variants, and analysis of these data may have important clinical implications for the treatment of patients with AI.

Rare case of serotonin syndrome with therapeutic doses of paroxetine.

Paroxetine (Paxil) is a selective serotonin reuptake inhibitor (SSRI) and anxiolytic that is approved to treat numerous mood disorders. Serotonin syndrome, defined as a triad of mental status changes, autonomic instability, and neuromuscular abnormalities, is a potentially life-threatening complication of administering such serotonin-modifying drugs. Most cases of serotonin syndrome that have occurred with paroxetine administration are due to inadvertent drug interactions, most notably between SSRIs and monamine oxidase inhibitors, or intentional overdoses. The authors present the case of an 80-year-old woman who presented with serotonin syndrome while on a therapeutic dose of paroxetine. Paroxetine was stopped, and aggressive hydration with fluids and treatment with cyproheptadine was followed by remarkable improvement and return to baseline status in 4 days. This case illustrates the importance for physicians to have a heightened sense of suspicion of the serotonin syndrome in any patient known to be on serotonin-modifying agents presenting with altered sensorium and cholinergic symptoms. Consequently, they will be able to start timely treatment without subjecting the patient to unnecessary and potentially harmful tests.

Fluticasone propionate/salmeterol hydrofluoroalkane via metered-dose inhaler with integrated dose counter: Performance and patient satisfaction.

Currently, patients have to keep track of doses to determine when to replace their metered-dose inhalers (MDIs). This study evaluated the performance and patient satisfaction of a novel MDI with an integrated dose counter. In an open-label study at 38 outpatient centres, patients > or =12 years old with asthma or chronic obstructive pulmonary disease (COPD) received two actuations of fluticasone propionate/salmeterol 125/25 microg (115/21 microg ex-actuator) hydrofluoroalkane (ADVAIR) HFA) via MDI with counter twice a day until all 120 actuations were completed. Concordance between counter and diary recordings in patients who reported use of > or =90% of labelled actuations (completer population, n = 228) was high (discrepancy rate of 0.94%) and the incidence of device firing without changes in counter readings was low (0.13%). Mean expected actuations based on canister weights (114) were slightly lower than mean counter (121) and diary reported actuations (120). Upon study completion, 95% of patients were satisfied with the dose counter and 92% agreed it would help prevent them from running out of medication. Safety assessments (intent-to-treat population, n = 237) indicated that the drug was well tolerated. This integrated MDI counter may help patients maintain better disease control by enabling them to accurately track their medication supply.

Comparative study of removal of Cr(VI) with PAC, GAC and adsorbent prepared from tobacco roots.

Tobacco roots activated carbon (TRAC) has been prepared from tobacco roots impregnated with 20% of ZnCl2 and carbonized at 6000 degrees C. Its adsorption capacity has been tested for the treatment of wastewater containing hexavalent chromium. The experiments were carried out in a batch process to study the different system variables such as concentration, adsorbent dosage and contact time. Removal of chromium in the process has been found to increase with increase in adsorbent dosage and contact time. The adsorption isotherm data fitted the Langmuir adsorption isotherm model.

Childhood parental loss and risk for first-onset of major depression and alcohol dependence: the time-decay of risk and sex differences.

BACKGROUND: Whereas a number of studies have suggested that parental loss is associated with increased risk for major depression (MD), much less is known about possible gender differences, diagnostic specificity and the time course of the impact of loss. METHOD: First-onsets for MD and alcohol dependence (AD) were assessed at personal interviews in 5070 twins from same-sex (SS) and 2118 from opposite-sex (OS) twin pairs ascertained from a population-based registry. Cox Proportional Hazard (PH) and Non-Proportional Hazard (NPH) models, examining first onsets of MD and AD, were used with twins from SS pairs and conditional logistic regression for OS pairs. Parent-child separations prior to age 17 were divided into death and separation from other causes. RESULTS: The PH assumptions of constant increased risk were rejected for the impact of loss on risk for MD but not for AD. NPH models found significantly increased risk for MD after both death and separation with the risk lasting much longer for separations. For AD, the PH model found significantly increased risk after parental separation but not death. In both SS and OS twin pairs, no sex differences were seen in the impact of parental loss on risk for MD whereas the association between separation and risk for AD was significantly stronger in females than in males. CONCLUSION: Consistent sex differences in the association with parental loss were seen for AD but not MD. The analysis of the time-course of increased risk after loss suggests three different patterns which may reflect different relationships: parental death and MD (return to baseline within approximately 12 years), separation and MD (return to baseline within approximately 30 years) and separation and AD (no change in risk over time).

Inhibition of p38 mitogen activated protein kinase increases lipopolysaccharide induced inhibition of apoptosis in neutrophils by activating extracellular signal-regulated kinase.

BACKGROUND: Prolonged polymorphonuclear neutrophil (PMN) survival has been implicated in tissue injury after sepsis. Previously we reported that lipopolysaccharide (LPS) inhibits PMN apoptosis via the activation of the extracellular signal-regulated kinase (ERK). Conversely, the p38 mitogen activated protein kinase (MAPK) pathway is involved in the spontaneous apoptosis of PMNs. The interaction between these 2 pathways and their ability to regulate apoptosis during sepsis remain largely undefined. We hypothesize that there is interaction between the ERK and p38 pathways during sepsis. METHODS: PMNs were isolated from healthy volunteers by Ficoll gradient centrifugation and red blood cell sedimentation. Cells were then pretreated for 1 hour with the ERK inhibitor (PD98059, 10 micromol/L), p38 inhibitor (SB203580, 1 micromol/L), or vehicle. After treatment with LPS, apoptosis and MAPK activity were correlated. RESULTS: LPS stimulation significantly inhibits PMN apoptosis compared with unstimulated cells. Furthermore, inhibition of ERK significantly abrogates this effect, whereas inhibition of p38 augments LPS induced inhibition of apoptosis. Elk-1 phosphorylation (ERK target) is significantly increased by LPS alone and by inhibition of the p38 pathway during LPS stimulation. This correlates with ERK phosphorylation by Western blot. CONCLUSIONS: These data show that p38 inhibition enhances ERK activity during endotoxemia. Furthermore, these data suggest that cooperation between ERK and p38 MAPK pathways dictates the apoptotic potential of PMNs during inflammatory states.

Mutation of the matrix metalloproteinase 2 gene (MMP2) causes a multicentric osteolysis and arthritis syndrome.

The inherited osteolyses or 'vanishing bone' syndromes are a group of rare disorders of unknown etiology characterized by destruction and resorption of affected bones. The multicentric osteolyses are notable for interphalangeal joint erosions that mimic severe juvenile rheumatoid arthritis (OMIMs 166300, 259600, 259610 and 277950). We recently described an autosomal recessive form of multicentric osteolysis with carpal and tarsal resorption, crippling arthritic changes, marked osteoporosis, palmar and plantar subcutaneous nodules and distinctive facies in a number of consanguineous Saudi Arabian families. We localized the disease gene to 16q12-21 by using members of these families for a genome-wide search for homozygous-by-descent microsatellite markers. Haplotype analysis narrowed the critical region to a 1.2-cM region that spans the gene encoding MMP-2 (gelatinase A, collagenase type IV; (ref. 3). We detected no MMP2 enzymatic activity in the serum or fibroblasts of affected family members. We identified two family-specific homoallelic MMP2 mutations: R101H and Y244X. The nonsense mutation effects a deletion of the substrate-binding and catalytic sites and the fibronectin type II-like and hemopexin/TIMP2 binding domains. Based on molecular modeling, the missense mutation disrupts hydrogen bond formation within the highly conserved prodomain adjacent to the catalytic zinc ion.

Heat shock protein 27 inhibits apoptosis in human neutrophils.

BACKGROUND: Prolonged neutrophil(PMN) survival has been implicated in tissue injury following sepsis. A variety of bacterial products have been identified which inhibit PMN apoptosis including lipopolysaccharide(LPS). Extracellular heat shock proteins(Hsp) have recently been identified as potent regulatory signals for the innate immune system during the inflammatory response. We hypothesized that Hsp 27 can affect PMN phenotype with respect to apoptosis and cytokine profile. MATERIALS AND METHODS: PMN were isolated from the peripheral blood of healthy human volunteers by red blood cell sedimentation and gradient centrifugation. Cells were placed in media and cultured for 18 h with and without recombinant human Hsp 27 at various concentrations. In parallel experiments, PMN were stimulated with LPS, a known inhibitor of PMN apoptosis, for comparison. Apoptosis was quantified using annexin V and propidium iodide staining with flow cytometric analysis. Culture supernatants were assayed for secretion of TNF-alpha, IL-10, and IL-12. RESULTS: Hsp 27 significantly inhibits PMN apoptosis [control; 81.8 +/- 3.6%, vs Hsp 27, 60.4 +/- 4.1% p < 0.05]. The reduction is similar to that signaled by LPS, alone. Together their effect is not synergistic. The Hsp 27 response is dose-dependent. Hsp 27 does not induce secretion of TNF-alpha, IL-10, or IL-12, whereas LPS does signal IL-12 and TNF-alpha secretion. CONCLUSION: These data demonstrate that exogenous Hsp 27 may play a role in neutrophil-mediated tissue injury during trauma and sepsis via its ability to inhibit neutrophil apoptosis. However, Hsp 27 does not significantly alter neutrophil phenotype with respect to cytokine production profile.

Protein kinase C inhibition abrogates hepatic ischemic preconditioning responses.

INTRODUCTION: A transient period of warm ischemia prior to a longer ischemic episode (ischemic preconditioning) protects the hepatic graft from cold ischemia. The mechanism for this protection is unknown, as is the role of protein kinase C in ischemic preconditioning responses. METHODS: Livers from 40 kg Yorkshire pigs were harvested and subjected to 2 h of cold ischemia (n = 6) (control). Another group of harvested livers was pretreated with a 15-min ischemic period followed by 15 min of in situ perfusion with (n = 5) or without (n = 5) a protein kinase C inhibitor, chelerythrine. Following cold ischemia, all grafts were reperfused on a perfusion circuit and the following variables evaluated: (1) hepatic graft function, (2) graft circulatory impairment, (3) hepatocellular damage, and (4) endothelial cell damage. Protein kinase C levels were also evaluated by Western blot in the cytoplasm of all grafts. RESULTS AND DISCUSSION: Ischemic preconditioned grafts demonstrate improved graft function, reduced graft circulatory impairment, and reduced endothelial cell damage as compared to cold ischemia controls. When preconditioned grafts were pretreated with chelerythrine, graft function, graft circulatory impairment, and endothelial cell damage were no different than cold ischemia controls. Ischemic preconditioned grafts demonstrated decreased levels of protein kinase C prior to cold ischemia. There was no change in protein kinase C levels in cold ischemia controls or chelerythrine-pretreated grafts prior to cold ischemia. These data indicate that modulation of protein kinase C is essential for ischemic preconditioning responses in the cold preserved hepatic graft.

The liver as an immune organ.

Systemic inflammation contributes to significant morbidity in the ICU. With its ability to generate antiinflammatory acute-phase proteins, cytokines via Kupffer cells, and recently acknowledged resident lymphocytes, the liver provides a central regulatory role in inflammation. The liver has constant exposure to foreign material as a result of gut translocation and first-pass metabolism from the bloodstream. Consequently, the balance between hepatic activation and tolerance becomes an important factor in the host response to inflammation. Interventions and therapies that can assess and modulate these hepatic functions can improve outcomes for ICU patients.