Summary: Chimeric antigen receptor (CAR) T‑cells are genetically engineered to give T‑cells the ability to attack specific cancer cells, and to improve outcome of patients with refractory/relapsed aggressive B‑cell malignancies. To date, several CAR T‑cell products are approved and additional products with similar indication or extended to other malignancies are currently being evaluated. Side effects of CAR T‑cell treatment are potentially severe or even life-threatening immune-related toxicities, specifically cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Consequently, medical emergency teams (MET) are increasingly involved in the assessment and management of CAR T‑cell recipients. This article describes the principles of CAR T‑cell therapy and summarizes the main complications and subsequent therapeutic interventions aiming to provide a survival guide for METs with a proposed management algorithm.

To evaluate the impact of active fluid de-resuscitation on mortality in critically ill patients with septic shock. A systematic search was performed on PubMed, EmBase, and the Cochrane Library databases. Trials investigating active fluid de-resuscitation and reporting data on mortality in patients with septic shock were eligible. The primary objective was the impact of active de-resuscitation in patients with septic shock on short-term mortality. Secondary outcomes were whether de-resuscitation lead to a fluid separation, and the impact of de-resuscitation on patient-centred outcomes. Thirteen trials (8,030 patients) were included in the systematic review, whereof 5 randomised-controlled trials (RCTs) were included in the meta-analysis. None of the RCTs showed a reduction in mortality with active de-resuscitation measures (relative risk (RR) 1.12 [95%-CI 0.84 - 1.48]). Fluid separation was achieved by two RCTs. Evidence from non-randomised trials suggests a mortality benefit with de-resuscitation strategies and indicates a trend towards a more negative fluid balance. Patient-centred outcomes were not influenced in the RCTs, and only one non-randomised trial revealed an impact on the duration of mechanical ventilation and renal replacement requirement (RRT). We found no evidence for superiority of active fluid de-resuscitation compared to usual care regarding mortality, fluid balance or patient-centred outcomes in patients with septic shock. Current evidence is limited by the lack of high-quality RCTs in patients with septic shock, the small sample sizes and the heterogeneity of the applied de-resuscitation techniques. In addition, validity of the majority of RCTs is compromised by their inability to achieve fluid separation.

Background: The detrimental impact of fluid overload (FO) on intensive care unit (ICU) morbidity and mortality is well known. However, research to identify subgroups of patients particularly prone to fluid overload is scarce. The aim of this cohort study was to derive “FO phenotypes” in the critically ill by using machine learning techniques. Methods: Retrospective single center study including adult intensive care patients with a length of stay of ≥3 days and sufficient data to compute FO. Data was analyzed by multivariable logistic regression, fast and frugal trees (FFT), classification decision trees (DT), and a random forest (RF) model. Results: Out of 1772 included patients, 387 (21.8%) met the FO definition. The random forest model had the highest area under the curve (AUC) (0.84, 95% CI 0.79–0.86), followed by multivariable logistic regression (0.81, 95% CI 0.77–0.86), FFT (0.75, 95% CI 0.69–0.79) and DT (0.73, 95% CI 0.68–0.78) to predict FO. The most important predictors identified in all models were lactate and bicarbonate at admission and postsurgical ICU admission. Sepsis/septic shock was identified as a risk factor in the MV and RF analysis. Conclusion: The FO phenotypes consist of patients admitted after surgery or with sepsis/septic shock with high lactate and low bicarbonate.

Emergency Departments (EDs) have to cope with an increasing number of elderly patients, often presenting with non-specific complaints (NSC), such as generalized weakness. Acute morbidity requiring early intervention is present in the majority of patients with NSC. Therefore, an early and optimal disposition plan is crucial. The objective of this study was to prospectively study the disposition process of patients presenting to the ED with NSC. For two years, all patients presenting with NSC presenting to an urban ED were screened and consecutively included. The initial disposition plan was compared to the effective transfer after observation. Optimal disposition was defined as a high accuracy regarding disposition of patients with acute morbidity to an internal medicine ward. The final study population consisted of 669 patients with NSC. Admission to internal medicine increased from 297 (44%) planned admissions to 388 (58%) effective admissions after observation. Conversely, transfers to geriatric community hospitals and discharges decreased from the initially planned 372 (56%) patients to 281 (42%) effectively transferred and discharged patients. The accuracy regarding disposition of patients with acute morbidity increased from 53% to 68% after observation. Disposition planning in patients with NSC improves after observation, if defined by the accuracy regarding hospitalization of patients with acute morbidity. Further research should focus on risk stratification tools for timely disposition planning in order to reduce high admission rates for patients without acute morbidity and high readmission rates for discharged patients with non-specific complaints.

Background Fluid overload is associated with excess mortality in septic shock. Current approaches to reduce fluid overload include restrictive administration of fluid or active removal of accumulated fluid. However, evidence on active fluid removal is scarce. The aim of this study is to assess the efficacy and feasibility of an early de-resuscitation protocol in patients with septic shock. Methods All patients admitted to the intensive care unit (ICU) with a septic shock are screened, and eligible patients will be randomised in a 1:1 ratio to intervention or standard of care. Intervention: Fluid management will be performed according to the REDUCE protocol, where resuscitation fluid will be restricted to patients showing signs of poor tissue perfusion. After the lactate has peaked, the patient is deemed stable and assessed for active de-resuscitation (signs of fluid overload). The primary objective of this study is the proportion of patients with a negative cumulative fluid balance at day 3 after ICU. Secondary objectives are cumulative fluid balances throughout the ICU stay, number of patients with fluid overload, feasibility and safety outcomes and patient-centred outcomes. The primary outcome will be assessed by a logistic regression model adjusting for the stratification variables (trial site and chronic renal failure) in the intention-to-treat population. Ethics and dissemination The study was approved by the respective ethical committees (No 2020–02197). The results of the REDUCE trial will be published in an international peer-reviewed medical journal regardless of the results. Trial registration number ClinicalTrials.gov, NCT04931485.