The association of premorbid conditions with 6-month mortality in acutely admitted ICU patients over 80 years.

BACKGROUND: Premorbid conditions influence the outcome of acutely ill adult patients aged 80 years and over who are admitted to the ICU. The aim of this study was to determine the influence of such premorbid conditions on 6 month survival. METHODS: Prospective cohort study in 242 ICUs from 22 countries including patients 80 years or above, admitted over a 6 months period to an ICU between May 2018 and May 2019. Only emergency (acute) ICU admissions in adult patients ≥ 80 years of age were eligible. Patients who were admitted after planned/elective surgery were excluded. We measured the Clinical Frailty Scale (CFS), the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), disability with the Katz activities of daily living (ADL) score, comorbidities and a Polypharmacy Score (CPS). RESULTS: Overall, the VIP2 study included 3920 patients. During ICU stay 1191 patients died (30.9%), and another 436 patients (11.1%) died after ICU discharge but within the first 30 days of admission, and an additional 895 patients died hereafter but within the first 6 months after admission (22.8%). The 6 months mortality was 64%. The median CFS was 4 (IQR 3-6). Frailty (CFS ≥ 5) was present in 26.6%. Cognitive decline (IQCODE above 3.5) was found in 30.2%. The median IQCODE was 3.19. A Katz ADL of 4 or less was present in 27.7%. Patients who surviving > 6 months were slightly younger (median age survivors 84 with IQR 81-86) than patients dying within the first 6 months (median age 84, IQR 82-87, p = 0.013), were less frequently frail (CFS > 5 in 19% versus 34%, p < 0.01) and were less dependent based on their Katz activities of daily living measurement (median Katz score 6, IQR 5-6 versus 6 points, IQR 3-6, p < 0.01). CONCLUSIONS: We found that Clinical Frailty Scale, age, and SOFA at admission were independent prognostic factors for 6 month mortality after ICU admission in patients age 80 and above. Adding other geriatric syndromes and scores did not improve the model. This information can be used in shared-decision making. CLINICALTRIALS: gov: NCT03370692.

COVID-19 Pandemic Did not Influence Number of Oncologic and Emergency Surgeries: A Retrospective Cohort Study from a Tertiary Hospital in Austria.

BACKGROUND: Many articles described a massive decline in surgical procedures during the COVID-19 pandemic waves. Especially the reduction in oncologic and emergency procedures led to the concern that delays and cancelling surgical activity might lead to a substantial increase in preventable deaths. METHODS: Overall numbers and types of surgery were analysed in a tertiary hospital in Austria during the winter period (October-April) from 2015/16 to 2021/22. The half-years 2019/20, 2020/21 and 2021/22 were defined as pandemic half-years and were compared with the mean results of the previous, four, pre-pandemic half-years. RESULTS: A reduction was found for overall numbers and elective surgeries during 2019/20 (4.62%; p < 0.0001 and 12.14; p < 0.0001 respectively) and 2021/22 (14.94%; p < 0.0001 and 34.27; p < 0.0001 respectively). Oncologic surgery increased during 2021/22 (- 12.59%; p < 0.0001) and remained unchanged during the other periods. Emergency surgeries increased during 2019/20 (- 6.97%; p < 0.0001) and during 2021/22 (- 9.44%; p < 0.0001) and remained unchanged during 2020/21. CONCLUSIONS: The concern that the pandemic led to a decrease in oncologic and emergency surgeries cannot be supported with the data from our hospital. A flexible, day-by-day, resource allocation programme with central coordination adhering to hospital resilience recommendations may have helped to adapt to the impact of the COVID-19 pandemic during the first three pandemic half-years.

[Hyponatremia : Etiology, diagnosis and acute therapy]. / Hyponatriämie : Ätiologie, Diagnostik und Akuttherapie.

Hyponatremia is one of the most common electrolyte disorders in emergency departments and hospitalized patients. Serum sodium concentration is controlled by osmoregulation and volume regulation. Both pathways are regulated via the release of antidiuretic hormone (ADH). Syndrome of inappropriate release of ADH (SIADH) may be caused by neoplasms or pneumonia but may also be triggered by drug use or drug abuse. Excessive fluid intake may also result in a decrease in serum sodium concentration. Rapid alteration in serum sodium concentration leads to cell swelling or cell shrinkage, which primarily causes neurological symptoms. The dynamics of development of hyponatremia and its duration are crucial. In addition to blood testing, a clinical examination and urine analysis are essential in the differential diagnosis of hyponatremia.

Characterising acute kidney injury: The complementary roles of biomarkers of renal stress and renal function.

PURPOSE: Although epidemiological studies have enhanced our understanding of acute kidney injury, defining the biologic processes corresponding to the clinical phenotype remains challenging. We have examined biomarkers associated with renal stress plus markers of glomerular function to assess whether this approach may aid prediction of AKI or other relevant endpoints. MATERIALS & METHODS: Urinary [TIMP-2]·[IGFBP7], serum creatinine, plasma cystatin C and plasma proenkephalin 119-159 2 were analyzed in patients enrolled in the prospective, international, Sapphire study. Heterogenous critically ill patients (n = 723) were examined with a primary endpoint of development of KDIGO stage 2-3 within 12 h and a secondary endpoint of major adverse kidney events at 30 days (MAKE30). RESULTS: 100 patients (14%) reached the primary endpoint. Markers of renal stress outperformed those associated with glomerular function. Combining [TIMP-2]•[IGFBP7] with serum creatinine, but not the other functional markers, significantly (p = 0.02) increased the area under the ROC curve (AUC) from 0.80 (0.76-0.84) to 0.85 (0.81-0.89). In patients who did not develop AKI, all markers of glomerular filtration, but not [TIMP-2]·[IGFBP7], were significantly elevated in patients with a history of CKD (p < 0.05). CONCLUSIONS: The combination of cell-cycle arrest biomarkers, TIMP-2 and IGFBP7, with serum creatinine but not cystatin C or PENK improved risk stratification for the development of stage 2 or 3 AKI over [TIMP-2]·[IGFBP7] alone.

Impact of COVID-19 on elective, emergency and oncological surgery during the first and the second wave in a tertiary university hospital : Have we learned the lessons?

BACKGROUND: The COVID-19 pandemic caused an important reduction in surgical activities during the first wave. Aim of this retrospective time-trend analysis was to examine whether also during the second wave in fall and winter 2020/2021 surgical interventions decreased. METHODS: Absolut numbers and types of surgeries in a tertiary university hospital during the second COVID-19 wave in fall/winter 2020/2021 were collected from the surgical planning software and compared with the same time frame over the last 5 years. In a second step, the reduction of surgical interventions during the second wave was compared with the reduction of surgical procedures during the first wave in spring 2020 at the same hospital. RESULTS: Despite a higher 7­day incidence of COVID-19 infection and a higher number of patients needing ICU treatment during the second wave, the reduction of surgical interventions was 3.22% compared to 65.29% during the first wave (p < 0.0001). Elective surgical interventions decreased by 88.63% during the first wave compared to 1.79% during the second wave (p < 0.0001). Emergency and oncological interventions decreased by 35.17% during the first wave compared to 5.15% during the second wave (p : 0.0007) and 47.59% compared to 3.89% (p < 0.0001), respectively. Surgical activity reduction in our institution was less pronounced despite higher occupancy of ICU beds during the second COVID-19 wave in fall/winter 2020/2021. CONCLUSION: Better understanding of the disease, adequate supply of disposables and improved interdisciplinary day by day management of surgical and ICU resources may have contributed to this improvement.

Differential procoagulatory response of microvascular, arterial and venous endothelial cells upon inflammation in vitro.

INTRODUCTION: Inflammation induces a procoagulant phenotype of endothelial cells (EC) with the exposure of tissue factor (TF), a potent initiator of the extrinsic coagulation cascade. Although systemic inflammation affects the whole vascular system, thrombotic lesions occur particularly in microcirculation. This raises the question of whether TF-procoagulant activity (TF-PCA) differs between EC from arterial, venous, and microvascular beds. MATERIALS AND METHODS: Functional coagulation tests, including TF-PCA, and inflammatory responses were investigated on arterial, venous and microvascular endothelial cells. Interleukin-6 (IL-6) and TF-levels were determined in cohort of 59 septic patients. RESULTS: We found that tumor necrosis factor alpha (TNFα), lipopolysaccharide, and interleukin-1ß induce a solid, dose-dependent increase in TF-PCA, which is highest in microvascular EC. A positive correlation of interleukin-6 (IL-6) with TF levels was observed in a cohort of 59 septic patients. In contrast, TF-PCA was independent of IL-6 concentrations in vitro. Re-analysis of publicly available gene expression data revealed that among the top 50 genes annotated to coagulation, TF is one of three regulated genes common to the three investigated EC subtypes. The response to inflammatory stimuli in terms of exposure of leukocyte-endothelial- and platelet-endothelial adhesion molecules (E-selectin and PECAM-1), remodeling of adherens junctions, co-exposure of negatively charged surfaces nor breakdown of the glycocalyx was comparable between the EC subtypes and did not explain the higher TF-PCA on microvascular cells. We found that the ratio of TF and TFPI exposure on the endothelial membrane significantly differs between the EC subtypes. CONCLUSIONS: These findings indicate that the ratio of TF to its inhibitor TFPI is a determinant of endothelial TF-PCA, which is most pronounced on microvascular endothelial cells and might explain why the microvascular system is particularly susceptible to inflammation-induced thrombosis.

Pathophysiology of COVID-19-associated acute kidney injury.

Although respiratory failure and hypoxaemia are the main manifestations of COVID-19, kidney involvement is also common. Available evidence supports a number of potential pathophysiological pathways through which acute kidney injury (AKI) can develop in the context of SARS-CoV-2 infection. Histopathological findings have highlighted both similarities and differences between AKI in patients with COVID-19 and in those with AKI in non-COVID-related sepsis. Acute tubular injury is common, although it is often mild, despite markedly reduced kidney function. Systemic haemodynamic instability very likely contributes to tubular injury. Despite descriptions of COVID-19 as a cytokine storm syndrome, levels of circulating cytokines are often lower in patients with COVID-19 than in patients with acute respiratory distress syndrome with causes other than COVID-19. Tissue inflammation and local immune cell infiltration have been repeatedly observed and might have a critical role in kidney injury, as might endothelial injury and microvascular thrombi. Findings of high viral load in patients who have died with AKI suggest a contribution of viral invasion in the kidneys, although the issue of renal tropism remains controversial. An impaired type I interferon response has also been reported in patients with severe COVID-19. In light of these observations, the potential pathophysiological mechanisms of COVID-19-associated AKI may provide insights into therapeutic strategies.

Postoperative acute kidney injury in adult non-cardiac surgery: joint consensus report of the Acute Disease Quality Initiative and PeriOperative Quality Initiative.

Postoperative acute kidney injury (PO-AKI) is a common complication of major surgery that is strongly associated with short-term surgical complications and long-term adverse outcomes, including increased risk of chronic kidney disease, cardiovascular events and death. Risk factors for PO-AKI include older age and comorbid diseases such as chronic kidney disease and diabetes mellitus. PO-AKI is best defined as AKI occurring within 7 days of an operative intervention using the Kidney Disease Improving Global Outcomes (KDIGO) definition of AKI; however, additional prognostic information may be gained from detailed clinical assessment and other diagnostic investigations in the form of a focused kidney health assessment (KHA). Prevention of PO-AKI is largely based on identification of high baseline risk, monitoring and reduction of nephrotoxic insults, whereas treatment involves the application of a bundle of interventions to avoid secondary kidney injury and mitigate the severity of AKI. As PO-AKI is strongly associated with long-term adverse outcomes, some form of follow-up KHA is essential; however, the form and location of this will be dictated by the nature and severity of the AKI. In this Consensus Statement, we provide graded recommendations for AKI after non-cardiac surgery and highlight priorities for future research.

Restrictive fluid management versus usual care in acute kidney injury (REVERSE-AKI): a pilot randomized controlled feasibility trial.

PURPOSE: We compared a restrictive fluid management strategy to usual care among critically ill patients with acute kidney injury (AKI) who had received initial fluid resuscitation. METHODS: This multicenter feasibility trial randomized 100 AKI patients 1:1 in seven ICUs in Europe and Australia. Restrictive fluid management included targeting negative or neutral daily fluid balance by minimizing fluid input and/or enhancing urine output with diuretics administered at the discretion of the clinician. Fluid boluses were administered as clinically indicated. The primary endpoint was cumulative fluid balance 72 h from randomization. RESULTS: Mean (SD) cumulative fluid balance at 72 h from randomization was - 1080 mL (2003 mL) in the restrictive fluid management arm and 61 mL (3131 mL) in the usual care arm, mean difference (95% CI) - 1148 mL (- 2200 to - 96) mL, P = 0.033. Median [IQR] duration of AKI was 2 [1-3] and 3 [2-7] days, respectively (median difference - 1.0 [- 3.0 to 0.0], P = 0.071). Altogether, 6 out of 46 (13%) patients in the restrictive fluid management arm and 15 out of 50 (30%) in the usual care arm received renal replacement therapy (RR 0.42; 95% CI 0.16-0.91), P = 0.043. Cumulative fluid balance at 24 h and 7 days was lower in the restrictive fluid management arm. The dose of diuretics was not different between the groups. Adverse events occurred more frequently in the usual care arm. CONCLUSIONS: In critically ill patients with AKI, a restrictive fluid management regimen resulted in lower cumulative fluid balance and less adverse events compared to usual care. Larger trials of this intervention are justified.

Outcomes in patients treated with chimeric antigen receptor T-cell therapy who were admitted to intensive care (CARTTAS): an international, multicentre, observational cohort study.

BACKGROUND: Chimeric antigen receptor (CAR) T-cell therapy can induce side-effects such as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome (ICANS), which often require intensive care unit admission. The aim of this study was to describe management of critically ill CAR T-cell recipients in intensive care. METHODS: This international, multicentre, observational cohort study was done in 21 intensive care units in France, Spain, the USA, the UK, Russia, Canada, Germany, and Austria. Eligible patients were aged 18 years or older; had received CAR T-cell therapy in the past 30 days; and had been admitted to intensive care for any reason. Investigators retrospectively included patients admitted between Feb 1, 2018, and Feb 1, 2019, and prospectively included patients admitted between March 1, 2019, and Feb 1, 2020. Demographic, clinical, laboratory, treatment, and outcome data were extracted from medical records. The primary endpoint was 90-day mortality. Factors associated with mortality were identified using a Cox proportional hazard model. FINDINGS: 942 patients received CAR T-cell therapy, of whom 258 (27%) required admission to intensive care and 241 (26%) were included in the analysis. Admission to intensive care was needed within median 4·5 days (IQR 2·0-7·0) of CAR T-cell infusion. 90-day mortality was 22·4% (95% CI 17·1-27·7; 54 deaths). At initial evaluation on admission, isolated cytokine release syndrome was identified in 101 patients (42%), cytokine release syndrome and ICANS in 93 (39%), and isolated ICANS in seven (3%) patients. Grade 3-4 cytokine release syndrome within 1 day of admission to intensive care was found in 50 (25%) of 200 patients and grade 3-4 ICANS in 38 (35%) of 108 patients. Bacterial infection developed in 30 (12%) patients. Life-saving treatments were used in 75 (31%) patients within 24 h of admission to intensive care, primarily vasoactive drugs in 65 (27%) patients. Factors independently associated with 90-day mortality by multivariable analysis were frailty (hazard ratio 2·51 [95% CI 1·37-4·57]), bacterial infection (2·12 [1·11-4·08]), and lifesaving therapy within 24 h of admission (1·80 [1·05-3·10]). INTERPRETATION: Critical care management is an integral part of CAR T-cell therapy and should be standardised. Studies to improve infection prevention and treatment in these high-risk patients are warranted. FUNDING: Groupe de Recherche Respiratoire en Réanimation Onco-Hématologique.

Frailty is associated with long-term outcome in patients with sepsis who are over 80 years old: results from an observational study in 241 European ICUs.

BACKGROUND: Sepsis is one of the most frequent reasons for acute intensive care unit (ICU) admission of very old patients and mortality rates are high. However, the impact of pre-existing physical and cognitive function on long-term outcome of ICU patients ≥ 80 years old (very old intensive care patients (VIPs)) with sepsis is unclear. OBJECTIVE: To investigate both the short- and long-term mortality of VIPs admitted with sepsis and assess the relation of mortality with pre-existing physical and cognitive function. DESIGN: Prospective cohort study. SETTING: 241 ICUs from 22 European countries in a six-month period between May 2018 and May 2019. SUBJECTS: Acutely admitted ICU patients aged ≥80 years with sequential organ failure assessment (SOFA) score ≥ 2. METHODS: Sepsis was defined according to the sepsis 3.0 criteria. Patients with sepsis as an admission diagnosis were compared with other acutely admitted patients. In addition to patients' characteristics, disease severity, information about comorbidity and polypharmacy and pre-existing physical and cognitive function were collected. RESULTS: Out of 3,596 acutely admitted VIPs with SOFA score ≥ 2, a group of 532 patients with sepsis were compared to other admissions. Predictors for 6-month mortality were age (per 5 years): Hazard ratio (HR, 1.16 (95% confidence interval (CI), 1.09-1.25, P < 0.0001), SOFA (per one-point): HR, 1.16 (95% CI, 1.14-1.17, P < 0.0001) and frailty (CFS > 4): HR, 1.34 (95% CI, 1.18-1.51, P < 0.0001). CONCLUSIONS: There is substantial long-term mortality in VIPs admitted with sepsis. Frailty, age and disease severity were identified as predictors of long-term mortality in VIPs admitted with sepsis.

Systemic inflammation as fuel for acute liver injury in COVID-19.

BACKGROUND: A cytokine storm conceivably contributes to manifestations of corona virus disease (COVID-19). Inflammatory cytokines such as interleukin-6 (IL-6) cause acute liver injury while serum detectability indicates systemic inflammation. AIMS: We explored a link between systemic IL-6, related acute phase proteins and liver injury in hospitalized COVID-19 patients. METHODS: 655 patients with suspected COVID-19 were screened in the emergency department at the University Hospital of Innsbruck, Austria, between February and April 2020. 96 patients (∼15%) were hospitalized with COVID-19. 15 patients required intensive-care treatment (ICT). Plasma aminotransferases, alkaline phosphatase, bilirubin, and gamma glutamyl transferase, as well as IL-6, C-reactive protein (CRP), ferritin and lactate dehydrogenase (LDH) were determined by standard clinical assays. RESULTS: Of all hospitalized COVID-19 patients, 41 (42%) showed elevated aspartate aminotransferase (AST) concentration. COVID-19 patients with elevated AST exhibited significantly higher IL-6 (p < 0.001), ferritin (p < 0.001), LDH (p < 0.001) and CRP (p < 0.05) serum concentrations compared to patients with normal AST. Liver injury correlated with systemic IL-6 (p < 0.001), CRP (p < 0.001), ferritin (p < 0.001) and LDH (p < 0.001) concentration. In COVID-19 patients requiring ICT, correlations were more pronounced. CONCLUSION: Systemic inflammation could be a fuel for hepatic injury in COVID-19.

Linkage of alterations in systemic iron homeostasis to patients' outcome in sepsis: a prospective study.

BACKGROUND: Sepsis, a dysregulated host response following infection, is associated with massive immune activation and high mortality rates. There is still a need to define further risk factors and laboratory parameters predicting the clinical course. Iron metabolism is regulated by both, the body's iron status and the immune response. Iron itself is required for erythropoiesis but also for many cellular and metabolic functions. Moreover, iron availability is a critical determinant in infections because it is an essential nutrient for most microbes but also impacts on immune function and intravascular oxidative stress. Herein, we used a prospective study design to investigate the putative impact of serum iron parameters on the outcome of sepsis. METHODS: Serum markers of iron metabolism were measured in a prospective cohort of 61 patients (37 males, 24 females) with sepsis defined by Sepsis-3 criteria in a medical intensive care unit (ICU) and compared between survivors and non-survivors. Regulation of iron parameters in patients stratified by focus of infection and co-medication as well as association of the markers with sepsis severity scores and survival were investigated with linear and logistic regression corrected for sex and age effects. RESULTS: Positive correlations of increased serum iron and ferritin concentrations upon ICU admission with the severity of organ failure (SOFA score) and with mortality were observed. Moreover, high TF-Sat, elevated ferritin and serum iron levels and low transferrin concentrations were associated with reduced survival. A logistic regression model consisting of SOFA and transferrin saturation (SOFA-TF-Sat) had the best predictive power for survival in septic ICU patients. Of note, administration of blood transfusions prior to ICU admission resulted in increased TF-Sat and reduced survival of septic patients. CONCLUSIONS: Our study could show an important impact of serum iron parameters on the outcome of sepsis. Furthermore, we identified transferrin saturation as a stand-alone predictor of sepsis survival and as a parameter of iron metabolism which may in a combined model improve the prediction power of the SOFA score. TRIAL REGISTRATION: The study was carried out in accordance with the recommendations of the Declaration of Helsinki on biomedical research. The study was approved by the institutional ethics review board of the Medical University Innsbruck (study AN2013-0006).

Identification and validation of biomarkers of persistent acute kidney injury: the RUBY study.

PURPOSE: The aim of the RUBY study was to evaluate novel candidate biomarkers to enable prediction of persistence of renal dysfunction as well as further understand potential mechanisms of kidney tissue damage and repair in acute kidney injury (AKI). METHODS: The RUBY study was a multi-center international prospective observational study to identify biomarkers of the persistence of stage 3 AKI as defined by the KDIGO criteria. Patients in the intensive care unit (ICU) with moderate or severe AKI (KDIGO stage 2 or 3) were enrolled. Patients were to be enrolled within 36 h of meeting KDIGO stage 2 criteria. The primary study endpoint was the development of persistent severe AKI (KDIGO stage 3) lasting for 72 h or more (NCT01868724). RESULTS: 364 patients were enrolled of whom 331 (91%) were available for the primary analysis. One hundred ten (33%) of the analysis cohort met the primary endpoint of persistent stage 3 AKI. Of the biomarkers tested in this study, urinary C-C motif chemokine ligand 14 (CCL14) was the most predictive of persistent stage 3 AKI with an area under the receiver operating characteristic curve (AUC) (95% CI) of 0.83 (0.78-0.87). This AUC was significantly greater than values for other biomarkers associated with AKI including urinary KIM-1, plasma cystatin C, and urinary NGAL, none of which achieved an AUC > 0.75. CONCLUSION: Elevated urinary CCL14 predicts persistent AKI in a large heterogeneous cohort of critically ill patients with severe AKI. The discovery of CCL14 as a predictor of persistent AKI and thus, renal non-recovery, is novel and could help identify new therapeutic approaches to AKI.

The contribution of frailty, cognition, activity of daily life and comorbidities on outcome in acutely admitted patients over 80 years in European ICUs: the VIP2 study.

PURPOSE: Premorbid conditions affect prognosis of acutely-ill aged patients. Several lines of evidence suggest geriatric syndromes need to be assessed but little is known on their relative effect on the 30-day survival after ICU admission. The primary aim of this study was to describe the prevalence of frailty, cognition decline and activity of daily life in addition to the presence of comorbidity and polypharmacy and to assess their influence on 30-day survival. METHODS: Prospective cohort study with 242 ICUs from 22 countries. Patients 80 years or above acutely admitted over a six months period to an ICU between May 2018 and May 2019 were included. In addition to common patients' characteristics and disease severity, we collected information on specific geriatric syndromes as potential predictive factors for 30-day survival, frailty (Clinical Frailty scale) with a CFS > 4 defining frail patients, cognitive impairment (informant questionnaire on cognitive decline in the elderly (IQCODE) with IQCODE ≥ 3.5 defining cognitive decline, and disability (measured the activity of daily life with the Katz index) with ADL ≤ 4 defining disability. A Principal Component Analysis to identify co-linearity between geriatric syndromes was performed and from this a multivariable model was built with all geriatric information or only one: CFS, IQCODE or ADL. Akaike's information criterion across imputations was used to evaluate the goodness of fit of our models. RESULTS: We included 3920 patients with a median age of 84 years (IQR: 81-87), 53.3% males). 80% received at least one organ support. The median ICU length of stay was 3.88 days (IQR: 1.83-8). The ICU and 30-day survival were 72.5% and 61.2% respectively. The geriatric conditions were median (IQR): CFS: 4 (3-6); IQCODE: 3.19 (3-3.69); ADL: 6 (4-6); Comorbidity and Polypharmacy score (CPS): 10 (7-14). CFS, ADL and IQCODE were closely correlated. The multivariable analysis identified predictors of 1-month mortality (HR; 95% CI): Age (per 1 year increase): 1.02 (1.-1.03, p = 0.01), ICU admission diagnosis, sequential organ failure assessment score (SOFA) (per point): 1.15 (1.14-1.17, p < 0.0001) and CFS (per point): 1.1 (1.05-1.15, p < 0.001). CFS remained an independent factor after inclusion of life-sustaining treatment limitation in the model. CONCLUSION: We confirm that frailty assessment using the CFS is able to predict short-term mortality in elderly patients admitted to ICU. Other geriatric syndromes do not add improvement to the prediction model. Since CFS is easy to measure, it should be routinely collected for all elderly ICU patients in particular in connection to advance care plans, and should be used in decision making.

Clinical use of [TIMP-2]•[IGFBP7] biomarker testing to assess risk of acute kidney injury in critical care: guidance from an expert panel.

BACKGROUND: The first FDA-approved test to assess risk for acute kidney injury (AKI), [TIMP-2]•[IGFBP7], is clinically available in many parts of the world, including the USA and Europe. We sought to understand how the test is currently being used clinically. METHODS: We invited a group of experts knowledgeable on the utility of this test for kidney injury to a panel discussion regarding the appropriate use of the test. Specifically, we wanted to identify which patients would be appropriate for testing, how the results are interpreted, and what actions would be taken based on the results of the test. We used a modified Delphi method to prioritize specific populations for testing and actions based on biomarker test results. No attempt was made to evaluate the evidence in support of various actions however. RESULTS: Our results indicate that clinical experts have developed similar practice patterns for use of the [TIMP-2]•[IGFBP7] test in Europe and North America. Patients undergoing major surgery (both cardiac and non-cardiac), those who were hemodynamically unstable, or those with sepsis appear to be priority patient populations for testing kidney stress. It was agreed that, in patients who tested positive, management of potentially nephrotoxic drugs and fluids would be a priority. Patients who tested negative may be candidates for "fast-track" protocols. CONCLUSION: In the experience of our expert panel, biomarker testing has been a priority after major surgery, hemodynamic instability, or sepsis. Our panel members reported that a positive test prompts management of nephrotoxic drugs as well as fluids, while patients with negative results are considered to be excellent candidates for "fast-track" protocols.