Figure 2 - available via license: Creative Commons Attribution-NonCommercial 4.0 International
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Different methods for extracorporeal blood purification therapies, each having a similar core and a variation to the technique with its physicochemical principles mentioned. The small arrows represented near the tubular structures show the flow of the blood, while the big arrow depicted from each method to the '?' represents the different variations of these methods.
Source publication
Recently, an increasing number of novel drugs were approved in oncology and hematology. Nevertheless, pharmacology progress comes with a variety of side effects, of which cytokine release syndrome (CRS) is a potential complication of some immunotherapies that can lead to multiorgan failure if not diagnosed and treated accordingly. CRS generally occ...
Context in source publication
Citations
... CRRT serves as the initial choice of RRT for 75% of critically ill patients [2,3]. Beyond renal replacement, CRRT finds extensive application across various critical clinical scenarios, including sepsis, poisoning, rhabdomyolysis, volume management, burns, multiple injuries, organ failure, and heatstroke [1,[4][5][6][7][8][9]. Notably, CRRT has garnered attention amidst the Coronavirus Disease 2019 (COVID-19) pandemic, further underscoring its versatile utility within the ICU setting [10][11][12][13][14]. Consequently, CRRT exhibits a promising scope of application within the ICU [15]. ...
... CRRT is an important organ support method that has been widely used in the field of critical care medicine [5,6,9,11,13,30]. To ensure patients receive precise and high-quality treatment, comprehensive investigations into all aspects of CRRT have been conducted. ...
Background
Continuous renal replacement therapy (CRRT) is a commonly utilized form of renal replacement therapy (RRT) in the intensive care unit (ICU). A specialized CRRT team (SCT, composed of physicians and nurses) engage playing pivotal roles in administering CRRT, but there is paucity of evidence-based research on joint training and management strategies. This study armed to evaluate the knowledge, attitude, and practice (KAP) of ICU staff toward CRRT, and to identify education pathways, needs, and the current status of CRRT implementation.
Methods
This study was performed from February 6 to March 20, 2023. A self-made structured questionnaire was used for data collection. Descriptive statistics, T-tests, Analysis of variance (ANOVA), multiple linear regression, and Pearson correlation coefficient tests (α = 0.05) were employed.
Results
A total of 405 ICU staff from 66 hospitals in Central and South China participated in this study, yielding 395 valid questionnaires. The mean knowledge score was 51.46 ± 5.96 (61.8% scored highly). The mean attitude score was 58.71 ± 2.19 (73.9% scored highly). The mean practice score was 18.15 ± 0.98 (85.1% scored highly). Multiple linear regression analysis indicated that gender, age, years of CRRT practice, ICU category, and CRRT specialist panel membership independently affected the knowledge score; Educational level, years of CRRT practice, and CRRT specialist panel membership independently affected the attitude score; Education level and teaching hospital employment independently affected the practice score. The most effective method for ICU staff to undergo training and daily work experience is within the department.
Conclusion
ICU staff exhibit good knowledge, a positive attitude and appropriately practiced CRRT. Extended CRRT practice time in CRRT, further training in a general ICU or teaching hospital, joining a CRRT specialist panel, and upgraded education can improve CRRT professional level. Considering the convenience of training programs will enhance ICU staff participation. Training should focus on basic CRRT principles, liquid management, and alarm handling.
... High levels of IL-6 can trigger pro-inflammatory IL-6 mediated signaling cascades, and IL-6 binding to soluble interleukin-6 receptors (sIL-6R), which can bind to gp130 of membrane proteins, consecutively activating the JAK-STAT pathway (87). In addition, due to the widespread expression of gp130 in many effector cells, high levels of IL-6 can lead to stronger immune activations (88). Research had found that the average level of IL-6 in patients with severe sepsis was significantly higher than that in healthy individuals (<10 pg./mL), which is tens or even hundreds of times higher than that of normal individuals (89). ...
Sepsis is a systemic inflammatory disease caused by severe infections that involves multiple systemic organs, among which the lung is the most susceptible, leaving patients highly vulnerable to acute lung injury (ALI). Refractory hypoxemia and respiratory distress are classic clinical symptoms of ALI caused by sepsis, which has a mortality rate of 40%. Despite the extensive research on the mechanisms of ALI caused by sepsis, the exact pathological process is not fully understood. This article reviews the research advances in the pathogenesis of ALI caused by sepsis by focusing on the treatment regimens adopted in clinical practice for the corresponding molecular mechanisms. This review can not only contribute to theories on the pathogenesis of ALI caused by sepsis, but also recommend new treatment strategies for related injuries.
... Future studies should focus on what is the real percentage of patients presenting with AKI and which one of the patients could be helped by initiating RRT early. RRT with Cytosorb ® or other hemadsorbers can be used as a bridge therapy for refractory CRS, as well as for managing sepsis, due to the elimination/adsorption of cytokines through the filter [33,34]. ...
Objective:
Our primary objective was to describe the baseline characteristics, main reasons for intensive care unit (ICU) admission, and interventions required in the ICU across patients who received CAR-T cell immunotherapy. The secondary objectives were to evaluate different outcomes (ICU mortality) across patients admitted to the ICU after having received CAR-T cell therapy.
Materials and methods:
We performed a medical literature review, which included MEDLINE, Embase, and Cochrane Library, of studies published from the inception of the databases until 2022. We conducted a systematic review with meta-analyses of proportions of several studies, including CAR-T cell-treated patients who required ICU admission. Outcomes in the meta-analysis were evaluated using the random-effects model.
Results:
We included four studies and analyzed several outcomes, including baseline characteristics and ICU-related findings. CAR-T cell recipients admitted to the ICU are predominantly males (62% CI-95% (57-66)). Of the total CAR-T cell recipients, 4% CI-95% (3-5) die in the hospital, and 6% CI-95% (4-9) of those admitted to the ICU subsequently die. One of the main reasons for ICU admission is acute kidney injury (AKI) in 15% CI-95% (10-19) of cases and acute respiratory failure in 10% CI-95% (6-13) of cases. Regarding the interventions initiated in the ICU, 18% CI-95% (13-22) of the CAR-T recipients required invasive mechanical ventilation during their ICU stay, 23% CI-95% (16-30) required infusion of vasoactive drugs, and 1% CI-95% (0.1-3) required renal replacement therapy (RRT). 18% CI-95% (13-22) of the initially discharged patients were readmitted to the ICU within 30 days, and the mean length of hospital stay is 22 days CI-95% (19-25). The results paint a current state of matter in CAR-T cell recipients admitted to the ICU.
Conclusions:
To better understand immunotherapy-related complications from an ICU standpoint, acknowledge the deteriorating patient on the ward, reduce the ICU admission rate, advance ICU care, and improve the outcomes of these patients, a standard of care and research regarding CAR-T cell-based immunotherapies should be created. Studies that are looking from the perspective of intensive care are highly warranted because the available literature regarding this area is scarce.
... This effect is most likely mediated through multiple mechanisms. Filtration of proinflammatory cytokines and heat loss in the extracorporeal circuit are some of the most important factors affecting body temperature [16][17][18][19][20][21]. Hypothermia occurs more commonly in patients on CKRT than in patients undergoing other modes of KRT, such as intermittent hemodialysis [22,23]. ...
Purpose
Continuous kidney replacement therapy (CKRT) is an increasingly common intervention for critically ill patients with kidney failure. Because CKRT affects body temperature, detecting infections in patients on CKRT is challenging. Understanding the relation between CKRT and body temperature may facilitate earlier detection of infection.
Methods
We retrospectively reviewed adult patients (≥ 18 years) admitted to the intensive care unit at Mayo Clinic in Rochester, Minnesota, from December 1, 2006, through November 31, 2015, who required CKRT. We summarized central body temperatures for these patients according to the presence or absence of infection.
Results
We identified 587 patients who underwent CKRT during the study period, of whom 365 had infections, and 222 did not have infections. We observed no statistically significant differences in minimum (P = .70), maximum (P = .22), or mean (P = .55) central body temperature for patients on CKRT with infection vs. those without infection. While not on CKRT (before CKRT initiation and after cessation), all three body temperature measurements were significantly higher in patients with infection than in those without infection (all P < .02).
Conclusion
Body temperature is insufficient to indicate an infection in critically ill patients on CKRT. Clinicians should remain watchful for other signs, symptoms, and indications of infection in patients on CKRT because of expected high infection rates.
... Sepsis leads to an imbalance in the internal and external environment of the body, as well as a significant disruption in the corresponding production of mediators, while the inflammatory mediators entering the circulatory system may have autocrine and paracrine effects. However, CRRT reduces these adverse effects of sepsis, effectively preventing further development of the inflammatory response, protecting tissue cells from damage by inflammatory factors, inhibiting the death of vascular endothelial cells, improving vascular function and hemodynamics, correcting vascular paralysis caused by sepsis, and improving tissue blood perfusion (Constantinescu et al. 2020). RBF patients presenting with hypercatabolism require adequate calorie and protein supplementation, while water intake needs to be restricted to avoid edema. ...
Sepsis is a series of systemic inflammatory reactions induced by infection and trauma, which can cause significant organ damage. Continuous renal replacement therapy (CRRT), a new alternative to renal therapy, is a long-term and continuous external blood purification therapy that lasts for 24 h. This procedure can remove metabolic toxins and inflammatory mediators in the body, as well as correct water electrolyte disorders and acid-base and immune imbalances. This article reviews the clinical application of CRRT in the treatment of sepsis-associated acute kidney injury and analyzes its underlying mechanisms in the treatment of sepsis, thereby providing a theoretical basis for the clinical treatment of sepsis.
Highlights Hemodynamic and non-hemodynamic mechanisms underlying sepsis-associated AKI.
Inflammatory and oxidative stress factors mediate AKI.
CRRT has therapeutic advantages and prospects in AKI.
... However, in the case of CAR-T therapy-mediated CRS, more efficient strategies are required, especially in the case of hematologic malignancies such as B-cell acute lymphoblastic leukemia (B-ALL) (235). IL-1 and IL-6 blockade, GM-CSF blockade, antibody-based immunotherapy pretreatment, therapeutic plasma exchange, hemofiltration, and fractionated CAR-T infusion are among strategies proven to be efficient in the management of severe lethal CRS after CAR-T therapy (235, [237][238][239][240][241][242][243][244][245]. Such strategies can also be applied in the case of solid tumor CAR-T therapy including TNBC CAR-T therapy. ...
Triple-negative breast cancer (TNBC) is known as the most intricate and hard-to-treat subtype of breast cancer. TNBC cells do not express the well-known estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) expressed by other breast cancer subtypes. This phenomenon leaves no room for novel treatment approaches including endocrine and HER2-specific antibody therapies. To date, surgery, radiotherapy, and systemic chemotherapy remain the principal therapy options for TNBC treatment. However, in numerous cases, these approaches either result in minimal clinical benefit or are nonfunctional, resulting in disease recurrence and poor prognosis. Nowadays, chimeric antigen receptor T cell (CAR-T) therapy is becoming more established as an option for the treatment of various types of hematologic malignancies. CAR-Ts are genetically engineered T lymphocytes that employ the body’s immune system mechanisms to selectively recognize cancer cells expressing tumor-associated antigens (TAAs) of interest and efficiently eliminate them. However, despite the clinical triumph of CAR-T therapy in hematologic neoplasms, CAR-T therapy of solid tumors, including TNBC, has been much more challenging. In this review, we will discuss the success of CAR-T therapy in hematological neoplasms and its caveats in solid tumors, and then we summarize the potential CAR-T targetable TAAs in TNBC studied in different investigational stages.
... Novel immunotherapies introduced in the fields of oncology and hematology are capable of inducing an HLH-like cytokine storm. The ones that are worth specifying are chimeric antigen receptor-modified T-cells (CAR-T cells), immune checkpoint inhibitors, and bi-specific T-cell engagers such as blinatumomab used for the treatment of B-acute lymphoblastic leukemia [6,56]. ...
... Nonetheless, a discussion can be held here, as it is often unknown whether HLH occurs as a paraneoplastic syndrome or a treatment-related condition. The recently approved treatment mentioned above is more likely to induce macrophage activation, and cytokine storms are often represented by CAR-T cells therapies or other T-cell-engaging therapies [56,61,62]. ...
... The patient was transferred to the ICU and started treatment with etoposide, high-dose dexamethasone, and hemodiafiltration, according to a previously published protocol [56]. Unfortunately, the patient died three days later. ...
Hemophagocytic lymphohistiocytosis (HLH) is a rare, elusive, and life-threatening condition that is characterized by the pathologic and uncontrolled secondary activation of the cytotoxic T-cells, natural killer cells (NK-cells), and macrophages of the innate immune system. This condition can develop in sporadic or familial contexts associated with hematological malignancies, as a paraneoplastic syndrome, or linked to an infection related to immune system deficiency. This leads to the systemic inflammation responsible for the overall clinical manifestations. Diagnosis should be thorough, and treatment should be initiated as soon as possible. In the current manuscript, we focus on classifying the HLH spectrum, describing the pathophysiology and the tools needed to search for and correctly identify HLH, and the current therapeutic opportunities. We also present the first case of a multiple myeloma patient that developed HLH following therapy with the ixazomib-lenalidomide-dexamethasone protocol.
... Using CRRT for immunomodulation has a long history in clinic for tapering cytokine storms and controlling the associated dysregulation of the immune system. This approach has also been proposed as adjuvant therapy in many diseases, including sepsis , septic AKI (Turani et al., 2019), septic shock (Schwindenhammer et al., 2019), severe Middle East Respiratory Syndrome (MERS) (Cha et al., 2015), severe acute pancreatitis (SAP) with or without ARDS (Cui et al., 2014;Gao et al., 2018), CRS induced by some immunotherapies (Constantinescu et al., 2020), severe burns (Peng et al., 2005), etc. Yet, a non-selective clearance allows harmful and beneficial substances to be simultaneously removed during CRRT (Shi et al., 2021). ...
In this study, we aimed to determine whether continuous renal replacement therapy (CRRT) with oXiris filter may alleviate cytokine release syndrome (CRS) in non-AKI patients with severe and critical coronavirus disease 2019 (COVID-19). A total of 17 non-AKI patients with severe and critical COVID-19 treated between February 14 and March 26, 2020 were included and randomly divided into intervention group and control group according to the random number table. Patients in the intervention group immediately received CRRT with oXiris filter plus conventional treatment, while those in the control group only received conventional treatment. Demographic data were collected and collated at admission. During ICU hospitalization, the concentrations of circulating cytokines and inflammatory chemokines, including IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ, were quantitatively measured daily to reflect the degree of CRS induced by SARS-CoV-2 infection. Clinical data, including the severity of COVID-19 white blood cell count (WBC), neutrophil proportion (NEUT%), lymphocyte count (LYMPH), lymphocyte percentage (LYM%), platelet (PLT), C-reaction protein (CRP), high sensitivity C-reactive protein (hs-CRP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TB), albumin (ALB), serum creatinine (SCr), D-Dimer, fibrinogen (FIB), IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ, number of hospital days and sequential organ failure assessment (SOFA) score were obtained and collated from medical records, and then compared between the two groups. Age, and SCr significantly differed between the two groups. Besides the IL-2 concentration that was significantly lower on day 2 than that on day 1 in the intervention group, and the IL-6 concentrations that were significantly higher on day 1, and day 2 in the intervention group compared to the control group, similar to the IL-10 concentration on day 5, there were no significant differences between the two groups. To sum up, CRRT with oXiris filter may not effectively alleviate CRS in non-AKI patients with severe and critical COVID-19. Thus, its application in these patients should be considered with caution to avoid increasing the unnecessary burden on society and individuals and making the already overwhelmed medical system even more strained (IRB number: IRB-AF/SC-04).
... The application of tocilizumab, an antibody against IL6 receptor, also exhibited protective role in patients suffered from grade II to III CAR-T induced CRS [187]. Corticosteroids, continuous renal replacement therapy (CRRT), delivery optimization for immunotherapies and next generation CAR-T (with ON−/OFFswitch components or multiple antigen targetted gates) are also recommended for CRS management [185,[188][189][190]. ...
Primary liver cancer (PLC) is a common malignancy with high morbidity and mortality. Poor prognosis and easy recurrence on PLC patients calls for optimizations of the current conventional treatments and the exploration of novel therapeutic strategies. For most malignancies, including PLC, immune cells play crucial roles in regulating tumor microenvironments and specifically recognizing tumor cells. Therefore, cellular based immunotherapy has its instinctive advantages in PLC therapy as a novel therapeutic strategy. From the active and passive immune perspectives, we introduced the cellular based immunotherapies for PLC in this review, covering both the lymphoid and myeloid cells. Then we briefly review the combined cellular immunotherapeutic approaches and the existing obstacles for PLC treatment.
... It is important to state that in this case, tocilizumab and glucocorticoids were not successful in controlling the mentioned adverse events (110). Furthermore, another study has also proposed that continuous renal replacement therapy (CRRT) can be an additional approach for controlling CAR-T therapy-related CRS that is resistant to conventional treatment (111). This study has demonstrated that CRRT is effective in mitigating sepsis which has a similar pathophysiological mechanism to CRS (111). ...
Chimeric antigen receptor T-cell (CAR-T) therapy has been successful in creating extraordinary clinical outcomes in the treatment of hematologic malignancies including relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). With several FDA approvals, CAR-T therapy is recognized as an alternative treatment option for particular patients with certain conditions of B-ALL, diffuse large B-cell lymphoma, mantle cell lymphoma, follicular lymphoma, or multiple myeloma. However, CAR-T therapy for B-ALL can be surrounded by challenges such as various adverse events including the life-threatening cytokine release syndrome (CRS) and neurotoxicity, B-cell aplasia-associated hypogammaglobulinemia and agammaglobulinemia, and the alloreactivity of allogeneic CAR-Ts. Furthermore, recent advances such as improvements in media design, the reduction of ex vivo culturing duration, and other phenotype-determining factors can still create room for a more effective CAR-T therapy in R/R B-ALL. Herein, we review preclinical and clinical strategies with a focus on novel studies aiming to address the mentioned hurdles and stepping further towards a milestone in CAR-T therapy of B-ALL.
