Advanced Organ Support Research Articles

Development and Validation of a Novel Pediatric Mechanical Circulatory Support Risk Stratification Tool: The Advanced Cardiac Therapies Improving Outcomes Network (ACTION) Ventricular Assist Device Score.

We sought to develop and validate a new risk stratification score for mortality for children supported with a ventricular assist device (VAD). This retrospective, multicenter study used data from patients undergoing VAD implantation between April 2018 and February 2023 at 44 participating institutions in the Advanced Cardiac Therapies Improving Outcomes (ACTION) network. Multivariable Cox proportional-hazards modeled mortality after VAD implantation. A total of 1,022 patients were enrolled. The 1 year mortality was 19% (95% confidence interval [CI]: 16-23). The multivariable model was used to build the ACTION VADs risk stratification score with four components: ventilation, advanced organ support (dialysis or ECMO), diagnosis, and size (weight ≤5 kg). One point is added for each risk factor. Based on the sum of the risk factors, patients were classified into four classes: class 0-green (4% mortality at 1 year), class 1-yellow (16% mortality at 1 year), class 2-orange (21% mortality at 1 year), and class 3 or higher-red (42% mortality at 1 year). The score performed well, with area under the curve (AUC) of 0.72 and excellent calibration. The ACTION VADs score for mortality can be calculated easily and offers risk stratification and prognostic information for pediatric VAD candidates. This is the first validated risk assessment tool for pediatric mechanical circulatory support.

The ADVanced Organ Support (ADVOS) hemodialysis system removes IL-6: an in vitro proof-of-concept study

BackgroundIL-6 is a pleiotropic cytokine modulating inflammation and metabolic pathways. Its proinflammatory effect plays a significant role in organ failure pathogenesis, commonly elevated in systemic inflammatory conditions. Extracorporeal blood purification devices, such as the Advanced Organ Support (ADVOS) multi hemodialysis system, might offer potential in mitigating IL-6's detrimental effects, yet its efficacy remains unreported.MethodsWe conducted a proof-of-concept in vitro study to assess the ADVOS multi system's efficacy in eliminating IL-6. Varying concentrations of IL-6 were introduced into a swine blood model and treated with ADVOS multi for up to 12 h, employing different blood and concentrate flow rates. IL-6 reduction rate, clearance, and dynamics in blood and dialysate were analyzed.ResultsIL-6 clearance rates of 0.70 L/h and 0.42 L/h were observed in 4 and 12-h experiments, respectively. No significant differences were noted across different initial concentrations. Reduction rates ranged between 40 and 46% within the first 4 h, increasing up to 72% over 12 h, with minimal impact from flow rate variations. Our findings suggest that an IL-6-albumin interaction and convective filtration are implicated in in vitro IL-6 elimination with ADVOS multi.ConclusionsThis study demonstrates for the first time an efficient and continuous in vitro removal of IL-6 by ADVOS multi at low blood flow rates. Initial concentration-dependent removal transitions to more consistent elimination over time. Further clinical investigations are imperative for comprehensive data acquisition.

Correlation between Bilirubin Elimination with the Cytokine Adsorber CytoSorb® and Mortality in Critically Ill Patients with Hyperbilirubinemia

Introduction: Hyperbilirubinemia is often the first evidence for any kind of liver disorder and over one-third of all patients in intensive care units (ICU) show elevated bilirubin concentrations. In critically ill patients, high concentrations of serum bilirubin are correlated with a poor outcome. Therapies to lower bilirubin concentrations are often just symptomatically and their effect on the patients’ outcome is hardly evaluated. Therefore, this study investigates whether the extracorporeal elimination of bilirubin with the cytokine adsorber CytoSorb^® (CS) reduces mortality in patients with hyperbilirubinemia. Methods: Patients with bilirubin concentrations >10 mg/dL at the ICU were screened for evaluation from 2018 to 2020. Patients with kidney replacement therapy and older than 18 years were included. Patients with continuously decreasing bilirubin concentrations after liver transplantation or other liver support systems (i.e., Molecular Adsorbents Recirculating System [MARS^®], Advanced Organ Support [ADVOS]) were excluded. CS therapy was used in clinical routine and was indicated by the treating physicians. Statistical analysis was performed with IBM SPSS statistics utilizing a multivariate model. Primary outcome measure was the effect of CS on the 30-day mortality. Results: Data from 82 patients (mean Simplified Acute Physiology Score [SAPS] II: 74 points, mean bilirubin: 18 mg/dL, mean lactate: 3.7 mmol/L) were analyzed. There were no significant differences in patients with and without CS treatment. The multivariate model showed no significant effect of CS therapy (p = 0.402) on the 30-day mortality. In addition, a significant effect of bilirubin concentration (p = 0.274) or Model for End-Stage Liver Disease score (p = 0.928) on the 30-day mortality could not be shown. In contrast, lactate concentration (p = 0.001, b = 0.044) and SAPS II (p = 0.025, b = 0.008) had significant impact on 30-day mortality. Conclusion: The use of CS in patients with hyperbilirubinemia did not result in a significant reduction in 30-day mortality. Randomized and controlled studies with mortality as primary outcome measure are needed in the future to justify their use.

Clinical Warburg effect in lymphoma patients admitted to intensive care unit

BackgroundThe Warburg effect, characterized by elevated lactate levels without tissue hypoxia or shock, has been described in patients with aggressive lymphoproliferative malignancies. However, the clinical characteristics and long-term outcomes in this population remain poorly understood.MethodsWe retrospectively analyzed 135 patients with aggressive lymphoproliferative malignancies admitted to the ICU between January 2017 and December 2022. Patients were classified into three groups: Clinical Warburg Effect (CWE), No Warburg with High Lactate level (NW-HL), and No Warburg with Normal Lactate level (NW-NL). Clinical characteristics and outcomes were compared between the groups and factors associated with 1-year mortality and CWE were identified using multivariable analyses.ResultsOf the 135 patients, 46 (34%) had a CWE. This group had a higher proportion of Burkitt and T cell lymphomas, greater tumor burden, and more frequent bone and cerebral involvement than the other groups. At 1 year, 72 patients (53%) died, with significantly higher mortality in the CWE and NW-HL groups (70% each) than in the NW-NL group (38%). Factors independently associated with 1-year mortality were age [HR = 1.02 CI 95% (1.00–1.04)], total SOFA score at admission [HR = 1.19 CI 95% (1.12–1.25)], and CWE [HR = 3.87 CI 95% (2.13–7.02)]. The main factors associated with the CWE were tumor lysis syndrome [OR = 2.84 CI 95% (1.14–7.42)], bone involvement of the underlying malignancy [OR = 3.58 CI 95% (1.02–12.91)], the total SOFA score at admission [OR = 0.81 CI 95% (0.69–0.91)] and hypoglycemia at admission [OR = 14.90 CI 95% (5.42–47.18)].ConclusionCWE is associated with a higher tumor burden and increased 1-year mortality compared to patients without this condition. Our findings underscore the importance of recognizing patients with CWE as a high-risk cohort, as their outcomes closely resemble those of individuals with lymphoma and shock, despite not requiring advanced organ support. Clinicians should recognize the urgency of managing these patients and consider early intervention to improve their prognosis.

Extracorporeal albumin dialysis in critically ill patients with liver failure: Comparison of four different devices-A retrospective analysis.

Besides standard medical therapy and critical care monitoring, extracorporeal liver support may provide a therapeutic option in patients with liver failure. However, little is known about detoxification capabilities, efficacy, and efficiency among different devices. Retrospective single-center analysis of patients treated with extracorporeal albumin dialysis. Generalized Estimating Equations with robust variance estimator were used to account for repeated measurements of several cycles and devices per patient. Between 2015 and 2021 n = 341 cycles in n = 96 patients were eligible for evaluation, thereof n = 54 (15.8%) treatments with Molecular Adsorbent Recirculating System, n = 64 (18.7%) with OpenAlbumin, n = 167 (48.8%) Advanced Organ Support treatments, and n = 56 (16.4%) using Single Pass Albumin Dialysis. Albumin dialysis resulted in significant bilirubin reduction without differences between the devices. However, ammonia levels only declined significantly in ADVOS and OPAL. First ECAD cycle was associated with highest percentage reduction in serum bilirubin. With the exception of SPAD all devices were able to remove the water-soluble substances creatinine and urea and stabilized metabolic dysfunction by increasing pH and negative base excess values. Platelets and fibrinogen levels frequently declined during treatment. Periprocedural bleeding and transfusion of red blood cells were common findings in these patients. From this clinical perspective ADVOS and OPAL may provide higher reduction capabilities of liver solutes (i.e. bilirubin and ammonia) in comparison to MARS and SPAD. However, further prospective studies comparing the effectiveness of the devices to support liver impairment (i.e. bile acid clearance or albumin binding capacity) as well as markers of renal recovery are warranted.

The Determining Factors for Outcome of Pediatric Intensive Care Admitted Children After Stem Cell Transplantation.

Requiring pediatric intensive care unit (PICU) admission relates to high mortality and morbidity in patients who received hematopoietic stem cell transplantation (HSCT). In this study, we aimed to evaluate the indications for PICU admission, treatments, and the determining risk factors for morbidity and mortality in patients who had allogeneic HSCT from various donors. In this retrospective study, we enrolled to patients who required the PICU after receiving allogeneic HSCT at our Pediatric Bone Marrow Transplantation Unit between 2005 and 2020. We evaluated to indication to PICU admission, applications, mortality rate, and the determining factors to outcomes. Thirty-three (7%) patients had 47 PICU admissions and 471 patients underwent bone marrow transplantation during 16-year study period. Also, 14 repeated episodes were registered in 9 different patients. The median age of PICU admitted patients was 4 (0.3 to 18) years and 29 (62%) were male. The main reasons for PICU admission were a respiratory failure, sepsis, and neurological event in 20, 8, and 7 patients, respectively. The average length of PICU stay was 14.5 (1 to 80) days, 14 (43%) of patients survived and the mortality rate was 57%. Multiple organ failure ( P =0.001), need for respiratory support ( P =0.007), inotrope agents ( P =0.001), and renal replacement therapy ( P =0.013) were found as significant risk factors for mortality. Allogeneic HSCT recipients need PICU admission because of its related different life-threatening complications. But there is a good chance of survival with quality PICU care and different advanced organ support methods.

Dynamics of disease characteristics and clinical management of critically ill COVID-19 patients over the time course of the pandemic: an analysis of the prospective, international, multicentre RISC-19-ICU registry

BackgroundIt remains elusive how the characteristics, the course of disease, the clinical management and the outcomes of critically ill COVID-19 patients admitted to intensive care units (ICU) worldwide have changed over the course of the pandemic.MethodsProspective, observational registry constituted by 90 ICUs across 22 countries worldwide including patients with a laboratory-confirmed, critical presentation of COVID-19 requiring advanced organ support. Hierarchical, generalized linear mixed-effect models accounting for hospital and country variability were employed to analyse the continuous evolution of the studied variables over the pandemic.ResultsFour thousand forty-one patients were included from March 2020 to September 2021. Over this period, the age of the admitted patients (62 [95% CI 60–63] years vs 64 [62–66] years, p < 0.001) and the severity of organ dysfunction at ICU admission decreased (Sequential Organ Failure Assessment 8.2 [7.6–9.0] vs 5.8 [5.3–6.4], p < 0.001) and increased, while more female patients (26 [23–29]% vs 41 [35–48]%, p < 0.001) were admitted. The time span between symptom onset and hospitalization as well as ICU admission became longer later in the pandemic (6.7 [6.2–7.2| days vs 9.7 [8.9–10.5] days, p < 0.001). The PaO2/FiO2 at admission was lower (132 [123–141] mmHg vs 101 [91–113] mmHg, p < 0.001) but showed faster improvements over the initial 5 days of ICU stay in late 2021 compared to early 2020 (34 [20–48] mmHg vs 70 [41–100] mmHg, p = 0.05). The number of patients treated with steroids and tocilizumab increased, while the use of therapeutic anticoagulation presented an inverse U-shaped behaviour over the course of the pandemic. The proportion of patients treated with high-flow oxygen (5 [4–7]% vs 20 [14–29], p < 0.001) and non-invasive mechanical ventilation (14 [11–18]% vs 24 [17–33]%, p < 0.001) throughout the pandemic increased concomitant to a decrease in invasive mechanical ventilation (82 [76–86]% vs 74 [64–82]%, p < 0.001). The ICU mortality (23 [19–26]% vs 17 [12–25]%, p < 0.001) and length of stay (14 [13–16] days vs 11 [10–13] days, p < 0.001) decreased over 19 months of the pandemic.ConclusionCharacteristics and disease course of critically ill COVID-19 patients have continuously evolved, concomitant to the clinical management, throughout the pandemic leading to a younger, less severely ill ICU population with distinctly different clinical, pulmonary and inflammatory presentations than at the onset of the pandemic.

Influence of Advanced Organ Support (ADVOS) on Cytokine Levels in Patients with Acute-on-Chronic Liver Failure (ACLF).

Background: ADVanced Organ Support (ADVOS) is a novel type of extracorporeal albumin dialysis that supports multiorgan function in patients with acute-on-chronic liver failure (ACLF). No data exist on whether ADVOS affects inflammatory cytokine levels, which play a relevant role in ACLF. Aim: Our aim was to quantify cytokine levels both before and after a single ADVOS treatment in patients with ACLF at a regular dialysis ward. Methods and results: In this prospective study, 15 patients (60% men) with ACLF and an indication for renal replacement therapy were included. Patient liver function was severely compromised, reflected by a median CLIF-consortium ACLF score of 38 (IQR 35; 40). Blood samples were directly taken before and after ADVOS dialysis. The concentration of cytokines for IL-1β, IFN-α2, IFN-γ, TNF-α, MCP-1, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-18, IL-23, IL-33 were quantified via a cytometric bead array. We found no significant (p > 0.05) change in cytokine levels, even when patients were stratified for dialysis time (<480 min versus ≥480 min). The relevance of the assessed cytokines in contributing to systemic inflammation in ACLF was demonstrated by Ingenuity pathway analysis®. Conclusion: Concentrations of pathomechanistically relevant cytokines remained unchanged both before and after ADVOS treatment in patients with ACLF.

The role of the ADVanced Organ Support (ADVOS) system in critically ill patients with multiple organ failure.

BackgroundMulti‐organ failure characterized by acute kidney injury, liver dysfunction, and respiratory failure is a complex condition associated with high mortality, for which multiple individual support devices may be simultaneously required. This review aims to appraise the current evidence for the ADVanced Organ Support (ADVOS) system, a novel device integrating liver, lung, and kidney support with blood detoxification.MethodsWe performed a literature review of the PubMed database to identify human and animal studies evaluating the ADVOS system.ResultsIn porcine models of acute liver injury and small clinical studies in humans, ADVOS significantly enhanced the elimination of water‐soluble and protein‐bound toxins and metabolites, including creatinine, ammonia, blood urea nitrogen, and lactate. Cardiovascular parameters (mean arterial pressure, cerebral perfusion pressure, and cardiac index) and renal function were improved. ADVOS clears carbon dioxide (CO2) effectively with rapid correction of pH abnormalities, achieving normalization of CO2, and bicarbonate levels. In patients with COVID‐19 infection, ADVOS enables rapid correction of acid–base disturbance and respiratory acidosis. ADVOS therapy reduces mortality in multi‐organ failure and has been shown to be safe with minimal adverse events.ConclusionsFrom the small observational studies analyzed, ADVOS demonstrates excellent detoxification of water‐soluble and protein‐bound substances. In particular, ADVOS permits the correction of metabolic and respiratory acidosis through the fluid‐based direct removal of acid and CO2. ADVOS is associated with significant improvements in hemodynamic and biochemical parameters, a trend toward improved survival in multi‐organ failure, and is well‐tolerated. Larger randomized trials are now necessary to further validate these encouraging results.

Application of bench studies at the bedside to improve outcomes in the management of severe diabetic ketoacidosis in children-a narrative review.

ObjectiveIn this review, we address a few key issues and the challenges faced in the management of severe diabetic ketoacidosis (DKA) in children, highlighting the existing standard of care, supported by evidence and bench studies.BackgroundThe classic triad of DKA namely hyperglycemia, metabolic acidosis and ketonemia warrants immediate attention with fluids and insulin. Correction of dehydration in DKA is of utmost priority and the calculation of fluid volume and choice of fluid have remained a matter of debate. Insulin therapy, to halt the ketone production, in DKA has undergone wide variations in dose and preparation since its discovery. Although the mortality due to severe DKA has remarkably decreased, complications like cerebral edema and acute kidney injury (AKI) continue to haunt the intensivists and endocrinologists on a few occasions.MethodsWe have selected a few important questions in the management of severe DKA in children, addressing the challenges, reviewing the studies, guidelines and bedside practices with evidence in this narrative review.ConclusionsThe focus of management should be to understand and normalise the deranged physiology rather than trying to get normal laboratory reports. This needs careful understanding of the pathogenesis and deriving conclusion from bench studies. With newer studies and evidence, guidelines are revised every few years. There is a trend towards more conservative therapy, with continuous and advanced monitoring. Switching to subcutaneous insulin and oral hydration is done as early as possible with clinical monitoring and resolution of DKA. Management of severe DKA in children can vary from simple fluid titration and insulin infusion in mild cases to a scenario with multiorgan dysfunction requiring intensive monitoring and advanced organ support. Individualisation of therapy to suit the needs with the available evidence and expertise is extremely essential.

Extracorporeal carbon dioxide removal with the Advanced Organ Support system in critically ill COVID-19 patients.

Disturbed oxygenation is foremost the leading clinical presentation in COVID‐19 patients. However, a small proportion also develop carbon dioxide removal problems. The Advanced Organ Support (ADVOS) therapy (ADVITOS GmbH, Munich, Germany) uses a less invasive approach by combining extracorporeal CO2‐removal and multiple organ support for the liver and the kidneys in a single hemodialysis device. The aim of our study is to evaluate the ADVOS system as treatment option in‐COVID‐19 patients with multi‐organ failure and carbon dioxide removal problems. COVID‐19 patients suffering from severe respiratory insufficiency, receiving at least two treatments with the ADVOS multi system (ADVITOS GmbH, Munich, Germany), were eligible for study inclusion. Briefly, these included patients with acute kidney injury (AKI) according to KDIGO guidelines, and moderate or severe ARDS according to the Berlin definition, who were on invasive mechanical ventilation for more than 72 hours. In total, nine COVID‐19 patients (137 ADVOS treatment sessions with a median of 10 treatments per patient) with moderate to severe ARDS and carbon dioxide removal problems were analyzed. During the ADVOS treatments, a rapid correction of acid‐base balance and a continuous CO2 removal could be observed. We observed a median continuous CO2 removal of 49.2 mL/min (IQR: 26.9‐72.3 mL/min) with some treatments achieving up to 160 mL/min. The CO2 removal significantly correlated with blood flow (Pearson 0.421; P < .001), PaCO2 (0.341, P < .001) and HCO3‐ levels (0.568, P < .001) at the start of the treatment. The continuous treatment led to a significant reduction in PaCO2 from baseline to the last ADVOS treatment. In conclusion, it was feasible to remove CO2 using the ADVOS system in our cohort of COVID‐19 patients with acute respiratory distress syndrome and multiorgan failure. This efficient removal of CO2 was achieved at blood flows up to 300 mL/min using a conventional hemodialysis catheter and without a membrane lung or a gas phase.

Numerical analysis of crimping behaviour of triaxial braided structures

The mechanical properties of tubular braided structures influence their inherent performance during application as biomedical materials. In their use as stents, braided structures are forced to conform to the topology of the host tissues. Triaxial braided structures have had limited use in tissue repair and organ support even though they have the potential of offering equal if not better performance compared to bi-axial braided structures. A study of the mechanical dynamics of tri-axial braids would be crucial in the potential design of customised structures for advanced tissue repair and organ support. This study therefore uses Finite Element Methods (FEM) to design and develop triaxial braided structures and investigate their crimping behaviour using parametric modeling and numerical analysis in their potential application as biomedical materials. The results in this study portrayed that the presence of axial yarns in tubular braided structure offers improved performance in terms of stability of the structure.

Pharmacokinetics of meropenem during advanced organ support (ADVOS®) and continuous renal replacement therapy.

The advanced organ support (ADVOS) system allows to eliminate water-soluble as well as protein-bound molecules. Despite its clinical features, to date nothing is known about the elimination of clinically relevant drugs such as antiinfectives. Therefore, we report a case treated with ADVOS, continuous renal replacement therapy (CRRT), and meropenem (1 g 8-hourly) for empiric sepsis therapy monitored by meropenem drug levels. ADVOS showed more efficient elimination of meropenem compared to CRRT which has to be considered when evaluating dosing regimens.

Successful elimination of bilirubin in critically ill patients with acute liver dysfunction using a cytokine adsorber and albumin dialysis: a pilot study

There are different methods of artificial liver support for patients with acute liver dysfunction (ALD). However, CytoSorb (CS) might be a new approved option for those patients. Question of interest is whether the elimination performance of CS was comparable to that of advanced organ support (ADVOS). Patients, treated with CS (integrated into high-flux dialysis) or ADVOS and a total bilirubin > 10 mg/dl were included. Laboratory parameters were evaluated before starting therapy (d0) and 12–24 h thereafter (d1). The Wilcoxon-test with associated samples was used for statistical analysis. Thirty-nine patients (33 CS, 6 ADVOS) were included. The median bilirubin at d0 was 16.9 and 17.7 mg/dl and at d1 was 13.2 and 15.9 mg/dl, in the CS and ADVOS group, respectively. There was a significant bilirubin reduction as well in the CS group (p < 0.001, median relative reduction: 22.5%) as in the ADVOS group (p = 0.028, median relative reduction: 22.8%). There was no significant difference in the relative bilirubin reduction between CS and ADVOS therapies. The use of CytoSorb and ADVOS in patients with ALD led to a significant and comparable decrease in total bilirubin. The easy use of CS might be an advantage compared to other procedures.

Applicability and safety of discontinuous ADVanced Organ Support (ADVOS) in the treatment of patients with acute-on-chronic liver failure (ACLF) outside of intensive care

ADVanced Organ Support (ADVOS) is a novel type of extracorporeal albumin dialysis and holds promise to sustain liver function and recovery of patients with acute-on-chronic liver failure (ACLF). Previously, ADVOS was tested as continuous treatment for intensive care patients with liver failure. Data related to the applicability and safety as discontinuous treatment outside of ICU is not available. Evaluation of ADVOS as discontinuous treatment for patients with ACLF outside intensive care unit and comparison with a matched historic cohort. In this retrospective study, 26 patients with ACLF and the indication for renal replacement therapy related to HRS-AKI were included. Majority of patients were male (65%) with alcoholic cirrhosis in 88% and infections as a trigger of ACLF in 96%. Liver function was severely compromised reflected by high median MELD and CLIF-C ACLF scores of 37 (IQR 32;40) and 56.5 (IQR 51;60), respectively. Patients were treated discontinuously with ADVOS over a median time of 12 days (IQR 8.25;17) and received 8 (IQR 4.25;9.75) treatment cycles on average. No treatment related adverse events were recorded, and safety laboratory parameters remained constant during the observation time. After 16 h cumulative dialysis therapy, ADVOS significantly reduced protein-bound bilirubin (14%), creatinine (11.8%) and blood urea nitrogen (BUN, 33%). Using a matched cohort with ACLF treated with hemodialysis, ADVOS achieved a stronger decrease in bilirubin (p = 0.01), while detoxification of water-soluble catabolites' including creatinine and BUN was comparable. The 28-days mortality in the ADVOS group was 56% (14/26) and was not inferior to predicted survival (predicted median 28-days mortality was 44%, IQR 30; 59). Discontinuous ADVOS treatment was safe and effective in patients with ACLF outside intensive care and outperformed hemodialysis in reducing protein-bound metabolites.

Applicability and safety of discontinuous ADVanced Organ Support (ADVOS) in the treatment of patients with acute-on-chronic liver failure (ACLF) outside of intensive care.

Applicability and safety of discontinuous ADVanced Organ Support (ADVOS) in the treatment of patients with acute-on-chronic liver failure (ACLF) outside of intensive care.

Registry on extracorporeal multiple organ support with the advanced organ support (ADVOS) system: 2-year interim analysis.

The objective of this registry is to collect data on real-life treatment conditions for patients for whom multiple organ dialysis with Advanced Organ Support (ADVOS) albumin hemodialysis is indicated.This registry was performed under routine conditions and without any study-specific intervention, diagnostic procedures, or assessments. Data on clinical laboratory tests, health status, liver function, vital signs, and examinations were collected (DRKS-ID: DRKS00017068). Mortality rates 28 and 90 days after the first ADVOS treatment, adverse events and ADVOS treatment parameters, including treatment abortions, were documented.This analysis was performed 2 years after the first patient was included on January 18, 2017. As of February 20, 2019, 4 clinical sites in Germany participated and enrolled 118 patients with a median age of 60 (IQR: 45, 69) of whom 70 were male (59.3%). Patients had a median SOFA Score of 14 (IQR: 11, 16) and a predicted mortality of 80%. The median number of failing organs was 3 (IQR: 2, 4).Four hundred twenty nine ADVOS treatments sessions were performed with a median duration of 17 hours (IQR: 6, 23). A 5.8% of the ADVOS sessions (25 of 429) were aborted due to device related errors, while 14.5% (62 of 429) were stopped for other reasons. Seventy nine adverse events were documented, 13 of them device related (all clotting, and all recovered without sequels).A significant reduction in serum creatinine (1.5 vs 1.2 mg/dl), blood urea nitrogen (24 vs 17 mg/dl) and bilirubin (6.9 vs 6.5 mg/dl) was observed following the first ADVOS treatment session. Blood pH, bicarbonate (HCO3-) and base excess returned to the physiological range, while partial pressure of carbon dioxide (pCO2) remained unchanged. At the time of the analysis, 28- and 90-day mortality were 60% and 65%, respectively, compared to an expected ICU-mortality rate of 80%. SOFA score was an independent predictor for outcome in a multivariable logistic regression analysis.The reported data show a high quality and completion of all participating centers. Data interpretation must be cautious due to the small number of patients, and the nature of the registry, without a control group. However, the data presented here show an improvement of expected mortality rates. Minor clotting events similar to other dialysis therapies occurred during the treatments.

A man in his sixties with dyspnoea following immunotherapy.

BACKGROUND Immunotherapy is a novel and effective treatment for many forms of cancer. However, side effects are different from those of classical chemotherapy, with risk of autoimmune reactions in normal tissue. Knowledge of these side effects is crucial in providing safe health care. CASE PRESENTATION A man in his sixties with metastatic renal cancer was admitted to hospital with dyspnoea 18 days after his first infusion with ipilimumab and nivolumab. He had started prednisolone two days earlier due to abnormal liver function tests and suspected autoimmune hepatitis. He had elevated troponin levels and severe arrhythmia. Endomyocardial biopsy showed lymphocytic infiltration indicating myocarditis. In the following days, he developed sensorimotor deficits and brain nerve dysfunction. He had fluctuating blood pressure, suggestive of autonomic failure. He developed respiratory failure despite normal thoracic CT scan and improvement in cardiac function. A comprehensive work-up revealed acute peripheral neuropathy. Despite advanced organ support and aggressive immunosuppressive treatment, the patient died 11 days after admission. INTERPRETATION Our patient died of a multi-system autoimmune reaction following the first dose of ipilimumab and nivolumab. This case illustrates the importance of monitoring these patients closely. Steroids and other immunosuppressant drugs should be started promptly on suspicion of adverse reaction.

Critically ill patients with cancer: A clinical perspective.

Cancer patients account for 15% of all admissions to intensive care unit (ICU) and 5% will experience a critical illness resulting in ICU admission. Mortality rates have decreased during the last decades because of new anticancer therapies and advanced organ support methods. Since early critical care and organ support is associated with improved survival, timely identification of the onset of clinical signs indicating critical illness is crucial to avoid delaying. This article focused on relevant and current information on epidemiology, diagnosis, and treatment of the main clinical disorders experienced by critically ill cancer patients.

Advanced organ support (ADVOS) in the critically ill: first clinical experience in patients with multiple organ failure

BackgroundPrevalence of multiple organ failure (MOF) in critically ill patients is increasing and associated mortality remains high. Extracorporeal organ support is a cornerstone in the management of MOF. We report data of an advanced hemodialysis system based on albumin dialysis (ADVOS multi device) that can regulate acid–base balance in addition to the established properties of renal replacement therapy and albumin dialysis systems in critically ill patients with MOF.Methods34 critically ill patients with MOF received 102 ADVOS treatment sessions in the Department of Intensive Care Medicine of the University Medical Center Hamburg-Eppendorf. Markers of metabolic detoxification and acid–base regulation were collected and blood gas analyses were performed. A subgroup analyses were performed in patients with severe acidemia (pH < 7.2).ResultsMedian number of treatment sessions was 2 (range 1–9) per patient. Median duration of treatment was 17.5 (IQR 11–23) hours per session. Treatment with the ADVOS multi-albumin dialysis device caused a significant decrease in bilirubin levels, serum creatinine, BUN and ammonia levels. The relative elimination rate of bilirubin was concentration dependent. Furthermore, a significant improvement in blood pH, HCO3− and PaCO2, was achieved during ADVOS treatment including six patients that suffered from severe metabolic acidosis refractory to continuous renal replacement therapy. Delta pH, HCO3− and PaCO2 were significantly affected by the ADVOS blood flow rate and pH settings. This improvement in the clinical course during ADVOS treatments allowed a reduction in norepinephrine during ADVOS therapy. Treatments were well tolerated. Mortality rates were 50% and 62% for 28 and 90 days, respectively.ConclusionsIn this case series in patients with MOF, ADVOS was able to eliminate water-soluble and albumin-bound substances. Furthermore, the device corrected severe metabolic and respiratory acid–base disequilibrium. No major adverse events associated with the ADVOS treatments were observed.