This study aims to investigate the effects of continuous renal replacement therapy (CRRT) combined with ulinastatin on cytokine levels and prognosis in patients with sepsis. The control and study groups (40 cases each) were established. The control group received CRRT alone, while the study group received CRRT plus ulinastatin treatment, with both groups being treated for 7 days. We compared the following parameters before and after treatment between the two groups: Sequential Organ Failure Assessment (SOFA) scores, Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, renal function indicators [cystatin C (CysC), blood urea nitrogen (BUN), and serum creatinine (SCr)], inflammatory factors [tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and procalcitonin (PCT)], and immune function parameters (CD4+, CD8+, CD4+/CD8+ ratio). Additionally, we recorded adverse reactions and 28-day mortality rates in both groups. After 7 days of treatment, the study group showed significantly lower SOFA scores, APACHE II scores, serum levels of CysC, BUN, Scr, TNF-α, CRP, PCT, and peripheral blood CD8+ compared to the control group, while demonstrating higher peripheral blood CD4+ and CD4+/CD8+ ratio. During the treatment period, there was no significant difference in the incidence of adverse reactions between the two groups. However, the 28-day mortality rate was significantly lower in the study group compared to the control group. For patients with sepsis, the combination of CRRT and ulinastatin therapy can significantly improve disease severity, inflammatory factors, renal function, and immune function, while reducing mortality rate.

While a dysregulated immune response is at the center of the sepsis definition, standard care is still solely focussed on prompt administration of antimicrobial therapy, source control, resuscitation and organ supportive therapies. Extracorporeal blood purification therapies, such as haemoadsorption, have been proposed as a possible adjunctive therapy to standard care in sepsis. These adsorption devices aim to rebalance the dysregulated immune response by removal of excessive amounts of circulating inflammatory mediators, including cytokines and endotoxins. Thus far, the effects of haemoadsorption on clinical outcomes have been insufficiently studied and although its routine use is not justified based on the current evidence, multiple centers use these devices in patients with severe septic shock. This narrative review describes the most well-studied adsorption devices as well as a novel selective adsorption device called the 'IL-6-Sieve', including in vitro data showing its capturing potential. Finally, it addresses important considerations for future trials on haemoadsorption in septic patients.

Background/Objectives: Sepsis, a life-threatening condition caused by a dysregulated immune response to infection, is associated with high mortality. Endotoxin and cytokine overload play a crucial role in sepsis-induced organ dysfunction. The Oxiris® membrane, traditionally used as a hemofilter for renal replacement therapy, has demonstrated the capacity to adsorb endotoxins and cytokines. This study investigates the clinical effect during hemoperfusion with the Oxiris® membrane in patients with septic shock and preserved renal function. Methods: We present three adult patients with septic shock who were admitted to the intensive care unit with high vasopressor requirements and elevated inflammatory markers. As they were refractory to standard therapy and renal function was preserved, a 12-hour hemoperfusion session with an Oxiris® membrane was initiated. Hemodynamic parameters, inflammatory biomarkers, and endotoxin concentrations were evaluated before, during, and after hemoperfusion treatment. Results: All patients demonstrated hemodynamic stabilization, with norepinephrine support reduced by 10.3% to 70.0%. Key inflammatory markers decreased significantly, including interleukin-6 (-41.6% to -94.0%), procalcitonin (-29.3% to -49.5%), and C-reactive protein (4.7% to -37.2%). Endotoxin concentrations decreased by 62.0% and 13.6% in two of the three patients. No adverse effects related to hemoperfusion were observed. Conclusions: Hemoperfusion with the Oxiris® membrane effectively reduced vasopressor support, inflammatory markers, and endotoxin concentrations in patients with refractory septic shock. This approach may offer a novel strategy for early immune modulation in sepsis before renal dysfunction occurs. Further studies with larger cohorts are required to validate these findings and determine optimal treatment protocols.

This study aimed to assess the clinical impact of oXiris-continuous hemofiltration adsorption on patients with septic shock and their prognosis.

A retrospective study.

Septic shock patients.

The oXiris group underwent hemofiltration adsorption using oXiris hemofilters and septic shock standard treatment, while the control group received septic shock standard treatment.

The changes in inflammatory indicators and short-term mortality rate were evaluated. Propensity score matching (PSM) was conducted based on the 1:2 ratio between the oXiris and control groups to account for any baseline data differences.

Results showed that after 24 h, 48 h, and 72 h of treatment, PCT, IL-6, and hs-CRP levels in the oXiris group were significantly lower than those in the control group (P < 0.05). However, there were no significant differences in norepinephrine equivalents and organ function status (APACHE II score, SOFA score, Lac) between the two groups at the same time points. The 72-h mortality rate (21.88% vs. 34.04%) and the 7-day mortality rate (28.12% vs. 44.68%) were lower in the oXiris group compared to the control group, but not statistically significant. The 28-day mortality rate did not show a significant difference between the two groups (53.19% vs. 56.25%).

oXiris continuous hemofiltration adsorption technology may reduce the levels of inflammatory factors in patients with septic shock; however, it does not appear to enhance organ function or improve the 28-day mortality rate in these patients.

This study reports the diagnosis and treatment of a 26-year-old pregnant woman with severe malnutrition combined with acute pyelonephritis causing sepsis, refractory septic shock and multiple organ failure. A female patient, 26 years old, was admitted to hospital mainly due to "menelipsis for more than 19 weeks, nausea and vomiting for 20 days, fever with fatigue for 3 days". At the end of 19 weeks of intrauterine pregnancy, the patient presented with fever accompanied by urinary tract irritation. Laboratory tests showed elevated inflammatory indicators, and ultrasonography showed bilateral pelvicalyceal dilation. She was diagnosed with acute pyelonephritis, sepsis, acute kidney injury (AKI) and severe malnutrition. After a whole-hospital consultation, the patient was treated with meropenem and vancomycin as antimicrobial therapy, and bilateral nephrostomy drainage was performed simultaneously. After that, the patient suffered a sudden decrease in blood pressure, blood oxygen saturation, and rapid heart rate. Septic shock with multiple organ dysfunction was considered, and she was transferred to intensive care unit (ICU) immediately. After the patient was transferred to ICU, emergency tracheal intubation and ventilator-assisted ventilation were performed. Rapid fluid resuscitation was administered for the patient. While pulse indicator continuous cardiac output (PICCO) monitoring was performed, norepinephrine, terlipressin, and methylene blue were administered to maintain peripheral vascular resistance. Since the patient developed septic cardiomyopathy and cardiogenic shock later, levosimendan and epinephrine were admi-nistered to improve cardiac function. While etiological specimens were delivered, meropenem, teicoplanin and caspofungin were given as initial empiric antimicrobial therapy. Unfortunately, the intrauterine fetal death occurred on the night of admission to ICU. On the 3rd day of ICU admission, a still-born child was delivered vaginally with 1/5 defect of the fetal membrane. On the 6th day of ICU admission, the patient had fever again with elevated inflammatory indicators. After excluding infection in other parts, intrau-terine infection caused by incomplete delivery of fetal membrane was considered. Then emergency uterine curettage was performed and the infection gradually improved. Later the laboratory results showed that the nephrostomy drainage was cultured for Escherichia coli and uterine, cervical and vaginal secretions were cultured for Candida albicans. Due to severe infection and intrauterine incomplete abortion, the patient developed disseminated intravascular coagulation (DIC). Active antimicrobial therapy and blood product supplement were given. However, the patient was critically ill with significant decrease in hemoglobin and platelets combined with multiple organ failure. Thrombotic microangiopathy (TMA) was not excluded yet, so plasma exchange was performed for the patient in order not to delay treatment. The patient underwent bedside continuous renal replacement therapy (CRRT) for AKI. The patient was complicated with acute liver injury, and the liver function gradually returned to normal after liver protection, antimicrobial therapy and other treatments. Due to the application of large doses of vasoactive drugs, the extremities of the patient gradually developed cyanosis and ischemic necrosis. Local dry gangrene of the bilateral toes remained at the time of discharge. In general, the patient suffered from septic shock, cardiogenic shock, combined with DIC and multiple organ dysfunction. After infection source control, antimicrobial therapy, uterine curettage, blood purification treatment, nutritional and metabolic support, the patient was discharged with a better health condition.

Some clinical trials have validated a new perspective on continuous renal replacement therapy (CRRT) in combination with oXiris haemofilter to more effectively enhance endotoxins clearance and circulating cytokines adsorption, stabilise vital signs, correct haemodynamic disorders and accelerate the recovery of organ function, thus providing survival benefits. However, no such combination mode has been reported in paediatric patients with sodium valproate (SV)-induced acute pancreatitis (AP).An early childhood boy was admitted to the department of critical care medicine, due to sudden upper abdominal pain lasting for 2 days. The child had a 2-year history of epilepsy and took 120 mg of SV two times per day for more than 2 months, after which he was diagnosed with the first episode of AP, bronchopneumonia and paroxysmal supraventricular tachycardia. The culprit of AP was identified as SV. After admission to the intensive care unit, the child immediately stopped taking SV and received comprehensive treatment for AP, followed by CRRT in combination with oXiris haemofilter. On the 3rd day after admission, a nasojejunal tube was implanted, followed by enteral nutrition, probiotics and levetiracetam. On the 22nd day after admission, the child was discharged from the hospital. At a 3-month follow-up after discharge, the child has returned to normal life without any sequelae.To the best of our knowledge, this is the first clinical case of SV-induced AP in a paediatric patient who achieved complete recovery after undergoing CRRT in combination with oXiris haemofilter, suggesting that this combination mode could be safely and effectively applied in patients with similar pathogenesis mechanisms as adjuvant therapy.

The application of high cutoff (HCO) membranes for continuous renal replacement therapy remains unclear in septic acute kidney injury (S-AKI) patients.

S-AKI patients who received continuous veno-venous hemodiafiltration (CVVHDF) were randomly assigned to the experimental group (HCO membrane) and the control group (high flux membrane, HF membrane). Interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in serum and waste fluid were measured at 0, 2, 12, and 24 h after CVVHDF initiation and the 28-day mortality.

Eleven patients were randomized to the HCO group, and 9 patients in the HF group, with a mean age of 54.9 ± 3.2 years and 6 patients (30%) being female. After 24 h of treatment with CVVHDF, there were significant reductions in serum IL-6 and TNF-α concentrations in the HCO group (p = 0.001, 0.015) and HF group (p = 0.004, 0.031). The serum IL-6 reduction rate of the HCO group was significantly higher than that of the HF group (79.21% vs. 42.69%, p = 0.025), while serum TNF-α reduction rates were comparable between the 2 groups. There were no significant changes in serum albumin after 24 h using either HCO membrane (28.7 ± 1.7 g/L vs. 32.7 ± 1.6 g/L, p = 0.138) or HF membrane (29.6 ± 1.1 g/L vs. 32.6 ± 1.3 g/L, p = 0.055). The two groups had similar 24-h filter clotting rates and 28-day mortality.

While CVVHDF with the HCO membrane and HF membrane both achieved significant reductions in serum cytokine levels, the HCO membrane was associated with a greater reduction rate in IL-6 but not in TNF-α. No difference was observed in serum albumin, mortality, or filter clotting.

Registry number: ChiCTR2000039725.

The 2012 Kidney Disease Improving Global Outcomes guidelines clearly define emergent indications for kidney replacement therapy; however, whether dialysis should be initiated in critically ill patients without these indications remains unclear. This review briefly summarizes the results of recent landmark trials and discusses their limitations originating from a criteria-based approach at a single time point. Moreover, a personalized approach based on each patient's demand-capacity balance and its future benefits as a platform for kidney support therapy in critically ill patients are discussed.

Cardiac arrest (CA) is a life-threatening event with a high mortality rate, and neurological injury following cardiopulmonary resuscitation (CPR) is a leading cause of death and disability in survivors. While prolonged CPR is often associated with poor neurological outcomes, there is limited evidence of successful recovery following extended resuscitation efforts. This study aims to highlight the potential for recovery after prolonged CPR by reporting a case of a patient who underwent 152 minutes of CPR, regained consciousness, and made a full recovery. The purpose is to explore whether advanced life-support techniques, such as extracorporeal CPR (ECPR), can improve survival and neurological outcomes even after prolonged CA.

A 53-year-old man with no prior health issues experienced sudden CA while exercising and underwent prolonged CPR.

Restoration of spontaneous circulation following CA and ventricular fibrillation.

ECPR, target temperature management, continuous renal replacement therapy, and intracranial pressure management.

Immediate recovery: following the restoration of spontaneous circulation, the patient was immediately transferred to the intensive care unit for further treatment. Despite the prolonged CPR duration, the patient remained hemodynamically stable and was able to tolerate the intensive interventions. Neurological recovery: after 1 week of intensive therapy, the patient regained consciousness. Initially, there was some confusion and disorientation, but he gradually became fully alert, oriented, and communicative. Neurological assessments indicated no significant long-term deficits, and brain imaging showed no signs of irreversible damage. Cardiological and renal recovery: cardiac function was closely monitored, with no evidence of significant ischemic damage to the myocardium. The patient's renal function improved with continuous renal replacement therapy, and kidney function returned to normal following the discontinuation of dialysis. Discharge: after 2 weeks of treatment in the intensive care unit and a transfer to the cardiology department for rehabilitation, the patient was discharged from the hospital. He had fully recovered both neurologically and physiologically, with no residual deficits.

This case demonstrates that prolonged CPR, when combined with advanced interventions such as ECPR, can result in favorable outcomes, including survival and neurological recovery. The findings suggest that with timely and appropriate treatment, even patients with extended resuscitation efforts may achieve full recovery, thus underscoring the potential of ECPR as a critical life-saving intervention in cases of prolonged CA.

BACKGROUND Extracorporeal blood purification strategies were recently developed as adjunctive treatments for sepsis. CytoSorb® is an approved medical device designed to reduce blood levels of inflammatory cytokines. The oXiris high-adsorption membrane filter is used in continuous hemofiltration adsorption. We describe the case of a 67-year-old man with recurrent septic shock, requiring treatment with antibiotics, vasopressors, inotropes, mechanical ventilation, continuous renal replacement therapy (CRRT), and adjunctive treatment with an oXiris filter and hemadsorption using the CytoSorb device. CASE REPORT A 67-year-old man was admitted to the Intensive Care Unit (ICU) with septic shock. He received antibiotics, fluids, vasopressors, and inotropes and was mechanically ventilated. Acute kidney failure was treated with CRRT. His condition improved, and he was transferred to the general ward. On day 3 in the ward, he developed a new episode of septic shock and was readmitted to ICU. Standard therapy with fluids, vasopressors, and empiric antibiotics was started. Despite treatment, his condition deteriorated dramatically. CRRT with an oXiris filter in combination with hemoadsorption using CytoSorb was started. After CRRT initiation and integration of the CytoSorb adsorber, rapid improvement in the patient's condition was observed. Daily laboratory test results showed significant decreases in procalcitonin and CRP. The patient was discharged from ICU on day 5 after initiation of CytoSorb therapy. CONCLUSIONS Although no guidelines and large clinical trial data are yet available to support the use of CytoSorb and oXiris, this report supports the findings from previous reports and small studies, that they can be considered as adjunctive treatments for patients with sepsis.

Background: Renal replacement therapy with an oXiris hemofilter may be helpful for patients with acute kidney injury in conjunction with sepsis and septic shock. The aim of this study was to assess the impact of an oXiris membrane on septic shock patients. Methods: All renal replacement therapies with oXiris (Baxter, Deerfield, IL, USA) performed between January 2018 and August 2021 were retrospectively analyzed. CRRT was initiated in continuous venovenous hemodiafiltration (CVVHDF) mode using Prismaflex System (Baxter). Demographic data, starting point of infection, source control, etiology, and course of treatment were analyzed. Results: A total of 32 patients were included in the study. Most patients treated with oXiris had acute kidney injury (AKI) and required CRRT. One patient had KDIGO 1 AKI (3.1%), three patients (9.4%) had KDIGO 2 AKI, and 28 patients (87.5%) had KDIGO 3 AKI. A statistically significant decrease in vasopressin dosage was required to achieve adequate MAP after 24 and 72 h, and a statistically significant decrease in norepinephrine dosage after 72 h was observed, with no SOFA score change on days 2 and 3. Procalcitonin and lactate levels did not change after 24 and 72 h. No beneficial effect on mortality was observed. Conclusions: Treatment with an oXiris membrane can positively impact vasopressors' requirement but not influence SOFA score, procalcitonin or lactate levels, or mortality in septic shock patients.

Sepsis represents a significant global health and hygiene challenge. Excessive activation of macrophages in sepsis can result in certain patients displaying characteristics akin to those observed in Macrophage Activation Syndrome (MAS). MAS represents a grave immune system disorder characterized by persistent and severe inflammation within the body. In the context of sepsis, MAS presents atypically, leading some researchers to refer to it as Macrophage Activation-Like Syndrome (MALS). However, there are currently no effective treatment measures for this situation. The purpose of this article is to explore potential treatment methods for sepsis-associated MALS.

The objective of this review is to synthesize the specific pathophysiological mechanisms and treatment strategies of MAS to investigate potential therapeutic approaches for sepsis-associated MALS.

We searched major databases (including PubMed, Web of Science, and Google Scholar etc.) for literature encompassing macrophage activation syndrome and sepsis up to Mar 2024 and combined with studies found in the reference lists of the included studies.

We have synthesized the underlying pathophysiological mechanism of MALS in sepsis, and then summarized the diagnostic criteria and the effects of various treatment modalities utilized in patients with MAS or MALS. In both scenarios, heterogeneous treatment responses resulting from identical treatment approaches were observed. The determination of whether the patient is genuinely experiencing MALS significantly impacts the ultimate outcomes of therapeutic efficacy. In order to tackle this concern, additional clinical trials and research endeavors are imperative.

Adsorption-based extracorporeal therapies have been subject to technical developments and clinical application for close to five decades. More recently, new technological developments in membrane and sorbent manipulation have made it possible to deliver more biocompatible extracorporeal adsorption therapies to patients with a variety of conditions. There are several key rationales based on physicochemical principles and clinical considerations that justify the application and investigation of such therapies as evidenced by multiple ex vivo, experimental and clinical observations. Accordingly, unspecific adsorptive extracorporeal therapies have now been applied to the treatment of a wide array of conditions from poisoning to drug overdoses, to inflammatory states and sepsis, and acute or chronic liver and kidney failure. In response to the rapidly expanding knowledge base and increased clinical evidence, we convened an Acute Disease Quality Initiative consensus conference dedicated to such treatment. The data show that hemoadsorption has clinically acceptable short-term biocompatibility and safety, technical feasibility and experimental demonstration of specified target molecule removal. Pilot studies demonstrate potentially beneficial effects on physiology and larger studies of endotoxin-based hemoadsorption have identified possible target phenotypes for larger randomized controlled trials. Moreover, in a variety of endogenous and exogenous intoxications, removal of target molecules has been confirmed in vivo. However, some studies have raised concerns about harm, or failed to deliver benefits. Thus, despite many achievements, modern hemoadsorption remains a novel and experimental intervention with limited data, and a large research agenda.

Cytokine-adsorption therapy has garnered attention as a potential treatment for conditions such as sepsis, although supporting evidence remains limited. Consequently, its utilization is expected to vary significantly across regions. To date, no ecological studies have investigated this regional heterogeneity.

This study aimed to examine temporal trends in the use of continuous renal replacement therapy (CRRT) with cytokine-adsorbing hemofilters and polymyxin-B immobilized fiber-direct hemoperfusion (PMX-DHP), as well as the spatial distribution of both across Japan's 47 prefectures.

This ecological study analyzed National Database (NDB) open data. A longitudinal analysis from 2016 to 2022 assessed temporal trends in the use of adsorption membranes. A cross-sectional analysis of the 2022 data utilized Moran's I statistic to evaluate the spatial autocorrelation of adsorption therapy. To examine the relationship between the two types of adsorption therapy, we calculated the Pearson correlation coefficient and conducted a multivariate analysis.

The longitudinal analysis revealed no significant change in the proportion of cytokine-adsorbing hemofilter use, while PMX-DHP use showed a decreasing trend over the seven-year period. Cross-sectional analysis indicated spatial autocorrelation for both PMX-DHP (Moran's I: 0.34, P < 0.001) and cytokine-adsorption filter use (Moran's I: 0.24, P < 0.001). Univariate analysis (R = -0.29, P = 0.0453) and multivariate analysis (estimated coefficient: 1.27, 95% CI: 0.06-2.49, P = 0.045) demonstrated that higher usage rates of cytokine-adsorbing blood filters were associated with higher PMX-DHP usage rates.

This study identified a declining trend in PMX-DHP use and an association between PMX-DHP and cytokine-adsorbing hemofilter utilization. These findings suggest that physicians' preferences and perceptions regarding cytokine-adsorption therapy may influence its use. Further research with individual patient data is warranted to confirm these findings.

Objective: The objective of this study is to assess and compare the efficacy of oXiris with conventional continuous renal replacement therapy (CRRT) in managing severe abdominal infections. Methods: A retrospective analysis encompassing cases from 2017 to 2023 was conducted at the Department of Critical Care Medicine within the First Affiliated Hospital of Fujian Medical University. Parameters including heart rate (HR), mean arterial pressure (MAP), oxygenation index, lactate (Lac), platelet count, neutrophil ratio, procalcitonin, C-reactive protein (CRP), interleukin 6 (IL-6), norepinephrine dosage, Acute Physiology and Chronic Health Evaluation II (APACHE II), and Sequential Organ Failure Assessment (SOFA) were recorded prior to treatment initiation, at 24 h, and 72 h after treatment for both the oXiris and conventional CRRT groups. In addition, the duration of respiratory support, CRRT treatment, length of stay in the intensive care unit (ICU), total hospitalization period, and mortality rates at 14 and 28 days for both groups were recorded. Results: 1) Within the conventional CRRT group, notable enhancement was observed solely in Lac levels at 24 h after treatment compared with pretreatment levels. In addition, at 72 h after treatment, improvements were evident in HR, Lac, CRP, and IL-6 levels. 2) Conversely, the oXiris group exhibited improvements in HR, MAP, Lac, oxygenation index, neutrophil ratio, and IL-6 at 24 h after treatment when compared with baseline values. In addition, reductions were observed in APACHE II and SOFA scores. At 72 h after treatment, all parameters demonstrated enhancement except for platelet count. 3) Analysis of the changes in the indexes (Δ) between the two groups at 24 h after treatment revealed variances in HR, MAP, Lac, norepinephrine dosage, CRP levels, IL-6 levels, APACHE II scores, and SOFA scores. 4) The Δ indexes at 72 h after treatment indicated more significant improvements following oXiris treatment for both groups, except for procalcitonin. 5) The 14-day mortality rate (24.4%) exhibited a significant reduction in the oXiris group when compared with the conventional group (43.6%). However, no significant difference was observed in the 28-day mortality rate between the two groups. 6) Subsequent to multifactorial logistic regression analysis, the results indicated that oXiris treatment correlated with a noteworthy decrease in the 14-day and 28-day mortality rates associated with severe abdominal infections, by 71.3% and 67.6%, respectively. Conclusion: oXiris demonstrates clear advantages over conventional CRRT in the management of severe abdominal infections. Notably, it reduces the fatality rates, thereby establishing itself as a promising and potent therapeutic option.

Clostridium perfringens can rarely cause severe systemic infections, usually from an abdominal source, associated with massive hemolysis, which is usually fatal. Hemolytic anemia and acute renal injury resulting from toxin action are critical for the development of multiple organ dysfunction syndrome (MODs), making this condition a real emergency, requiring multispecialty skills and aggressive multimodal therapies. We herein describe a case of septic shock from acute cholecystitis with massive hemolysis caused by C. perfringens in a 55 year-old man that was successfully treated with early blood purification and continuous renal replacement therapy (CRRT) along with antibiotic therapy and surgery. The effect of the enormous amount of toxins produced by Clostridium which elicit a strong cytokine response and the damage caused by the hemolysis products are the main pathogenetic mechanisms of this rare but lethal clinical entity. The main goal of treatment is to remove toxins from plasma, block toxin action, and further production by achieving bacterial killing with antimicrobial agents and controlling the infectious focus, remove waste products and prevent or limit multiorgan damage. Blood purification techniques play an important role due to a strong pathophysiological rationale, as they can remove toxins and cytokines as well as cell-free products from plasma and also replace renal function. Although this condition is rare and robust data are lacking, blood purification techniques for C. perfringens-induced massive hemolysis are promising and should be further explored.

Castleman disease (CD) is a rare lymphoproliferative disorder, with non-specific clinical manifestations, often delayed diagnosis and treatment, which pose a significant challenge in the present times. Patients diagnosed with this disease have poor prognosis due to the limited treatment options. Multicentric CD occurs at multiple lymph node stations and is associated with a proinflammatory response that leads to the development of the so-called 'B symptoms'. IL-6 seems to be a key cytokine involved in various manifestations such as lymphadenopathies, hepatosplenomegaly, and polyclonal hypergammaglobulinemia. Its levels correlate with the activity of the disease. Other consequences of MCD include increased fibrinogen levels leading to deep vein thrombosis and thromboembolic disorders, high hepcidin levels causing anaemia, elevated VEGF levels promoting angiogenesis and vascular permeability, which, along with hypoalbuminemia, induce oedema, ascites, pleural and pericardial effusions, and in severe cases, generalized anasarca. In extreme cases multiple organ failure can occur, often resulting in death. We propose the use of continuous renal replacement therapy (CRRT) in managing severe multicentric CD. Our arguments are based on the principles that CRRT is able to remove IL-6 from circulation thus attenuating the cytokine storm, can influence hepcidin levels, and reduction in oedema, and is often used in multiple organ failure to regain homeostasis control. Therefore, it could be used as a therapy or bridge therapy in severe cases. To sustain our hypothesis with evidence, we have gathered several studies from the literature confirming the successful removal of cytokines, especially IL-6 from circulation, which can be used as a starting point.

The clinical effectiveness of Oxiris®, particularly in reducing cytokines, remains uncertain due to the limited data provided. This study explored and analyzed the application value of Oxiris® endotoxin adsorption technology in a large animal model. Pigs received an intravenous LPS infusion. Six animals were treated 2 h after the infusion with an Oxiris® hemadsorption using a pumpless extracorporeal technique for 6 h. Five animals served as controls. Cardiocirculatory parameters, hyperspectral analysis, and a panel of cytokines were measured. The lipopolysaccharide infusion induced sepsis-like inflammation with tachycardia, elevated pulmonary pressure, elevated lactate level, as well as elevated pro-inflammatory cytokines like interferon (IFN)-γ, interleukin (IL)-1β, IL-2, IL-6, IL-8, IL-12 and tumor necrosis factor alpha (TNF-α). In addition, increases of anti-inflammatory cytokines like IL-1ra and IL-10 were found. After 3 and 6 h in both groups, pro-inflammatory cytokines were significantly reduced. No differences between the intervention and the control group could be detected after 3 and 6 h for IL-1β, IL-2, IL-6, IL-8, IL-12 and TNF-α, suggesting no effect of the Oxiris® filter on the elimination of elevated cytokines with a pumpless extracorporeal hemadsorption technique. The presented large animal model may be a promising option for studying the effects of hemadsorption techniques.

Sepsis, one of the leading causes of death, is still lacking specific treatment. OXIRIS (BAXTER, Deerfield, IL, USA) is the first device allowing combined removal of endotoxins, inflammatory mediators and uremic toxins, alongside fluid balance control. Available data is very limited. This retrospective propensity score-matched cohort study of adult patients with septic shock aimed to evaluate septic shock duration and mortality in patients treated with either standard of care renal replacement therapy (RRT) or RRT with combined hemoadsorption, who were admitted to the interdisciplinary surgical intensive care unit at Heidelberg University Hospital during the years 2018 through 2021. Main outcomes were duration of shock, thirty-day mortality and plasma interleukin-6 levels before and after initiation of hemoadsorption. Included were 117 patients (female, 33%; male 67%); median age: 67 (16) years. After matching: 42 patients (female, 33%; male, 67%); mean age: 59.1 ± 13.8 years. There was no statistically significant difference in septic shock duration (p = 0.94; hazard ratio (HR) 0.97 (95% CI, 0.48-1.97)). Thirty-day survival analysis showed a non-statistically significant survival difference. (p = 0.063; HR 0.43 (95% CI, 0.17-1.09)). A post-hoc 90-day survival analysis revealed statistically significant longer survival and lower death hazard ratio in patients treated with RRT + HA (p = 0.037; HR = 0.42 (95% CI, 0.18-0.99). In conclusion, RRT with combined hemoadsorption of endotoxins, inflammatory mediators and uremic toxins is a modality worth further investigation.

Sepsis poses a significant threat to human health due to its high morbidity and mortality rates worldwide. Traditional diagnostic methods for identifying sepsis or its causative organisms are time-consuming and contribute to a high mortality rate. Biomarkers have been developed to overcome these limitations and are currently used for sepsis diagnosis, prognosis prediction, and treatment response assessment. Over the past few decades, more than 250 biomarkers have been identified, a few of which have been used in clinical decision-making. Consistent with the limitations of diagnosing sepsis, there is currently no specific treatment for sepsis. Currently, the general treatment for sepsis is conservative and includes timely antibiotic use and hemodynamic support. When planning sepsis-specific treatment, it is important to select the most suitable patient, considering the heterogeneous nature of sepsis. This comprehensive review summarizes current and evolving biomarkers and therapeutic approaches for sepsis.

Sepsis and septic shock are associated with high mortality, with diagnosis and treatment remaining a challenge for clinicians. Their management classically encompasses hemodynamic resuscitation, antibiotic treatment, life support, and focus control; however, there are aspects that have changed. This narrative review highlights current and avant-garde methods of handling patients experiencing septic shock based on the experience of its authors and the best available evidence in a context of uncertainty. Following the first recommendation of the Surviving Sepsis Campaign guidelines, it is recommended that specific sepsis care performance improvement programs are implemented in hospitals, i.e., "Sepsis Code" programs, designed ad hoc, to achieve this goal. Regarding hemodynamics, the importance of perfusion and hemodynamic coherence stand out, which allow for the recognition of different phenotypes, determination of the ideal time for commencing vasopressor treatment, and the appropriate fluid therapy dosage. At present, this is not only important for the initial timing, but also for de-resuscitation, which involves the early weaning of support therapies, directed elimination of fluids, and fluid tolerance concept. Finally, regarding blood purification therapies, those aimed at eliminating endotoxins and cytokines are attractive in the early management of patients in septic shock.

Apheresis is a modern medical approach in which plasma or cellular components are separated from the whole blood. Apheresis can be either diagnostic or therapeutic. Diagnostic apheresis is typically applied in hematology and cancer research. Therapeutic Apheresis (TA) includes a broad spectrum of extracorporeal treatments applied in various medical specialties, including Intensive Care Unit (ICU). Considering the complexity of the pathophysiologic characteristics of various clinical entities and in particular sepsis, apheresis methods are becoming increasingly applicable. Therapeutic Plasma Exchange (TPE) is the most common used method in ICU. It is considered as first line therapy for Thrombotic Thrombocytopenic Purpura (TTP) and Guillain Barre Syndrome, while the current data for sepsis are scarce. Over the last decades, technologic evolution has led to increasing application of new and more selective methods based on adsorptive techniques. In this review we will describe the current data of characteristics of different techniques, safety and clinical impact of apheresis methods used in ICUs.

To investigate the efficacy and safety of continuous blood purification (CBP) in neonates with septic shock and acute kidney injury (AKI). This retrospective study was conducted at two tertiary care children's hospitals between January 2015 and May 2022. A total of 26 neonates with septic shock and AKI were included in this study, with a mortality rate of 50%. Fourteen neonates (53.8%) received continuous veno-venous hemodiafiltration, and 12 (46.2%) received continuous veno-venous hemofiltration. Compared with the indices before CBP, urine output increased 12 h after CBP initiation (P = 0.003) and serum creatinine decreased (P = 0.019). After 24 h of CBP, blood urea nitrogen had decreased (P = 0.006) and mean arterial pressure had increased (P = 0.007). At the end of CBP, the vasoactive-inotropic score and blood lactate were decreased (P = 0.035 and 0.038, respectively) and PH was increased (P = 0.015). Thrombocytopenia was the most common complication of CBP.  Conclusion: CBP can efficiently maintain hemodynamic stability, improve renal function, and has good safety in neonates with septic shock and AKI. However, the mortality rate remains high, and whether CBP improves the prognosis of neonates with septic shock and AKI remains unclear. What is Known: • Over 50% of children with septic shock have severe AKI, of which 21.6% required CBP. • The clinical application of CBP in septic shock has attracted increasing attention. What is New: • CBP can efficiently maintain hemodynamic stability, improve renal function, and has good safety in neonates with septic shock and AKI. • The mortality rate in neonates with septic shock and AKI receiving CBP remains high.

Endotoxin adsorption is a promising but controversial therapy in severe, refractory septic shock and conflicting results exist on the effective capacity of available devices to reduce circulating endotoxin and inflammatory cytokine levels.

Multiarm, randomized, controlled trial in two Swiss intensive care units, with a 1:1:1 randomization of patients suffering severe, refractory septic shock with high levels of endotoxemia, defined as an endotoxin activity ≥ 0.6, a vasopressor dependency index ≥ 3, volume resuscitation of at least 30 ml/kg/24 h and at least single organ failure, to a haemoadsorption (Toraymyxin), an enhanced adsorption haemofiltration (oXiris) or a control intervention. Primary endpoint was the difference in endotoxin activity at 72-h post-intervention to baseline. In addition, inflammatory cytokine, vasopressor dependency index and SOFA-Score dynamics over the initial 72 h were assessed inter alia.

In the 30, out of 437 screened, randomized patients (10 Standard of care, 10 oXiris, 10 Toraymyxin), endotoxin reduction at 72-h post-intervention-start did not differ among interventions (Standard of Care: 12 [1-42]%, oXiris: 21 [10-51]%, Toraymyxin: 23 [10-36]%, p = 0.82). Furthermore, no difference between groups could be observed neither for reduction of inflammatory cytokine levels (p = 0.58), nor for vasopressor weaning (p = 0.95) or reversal of organ injury (p = 0.22).

In a highly endotoxemic, severe, refractory septic shock population neither the Toraymyxin adsorber nor the oXiris membrane could show a reduction in circulating endotoxin or cytokine levels over standard of care. Trial registration ClinicalTrials.gov. NCT01948778. Registered August 30, 2013. https://clinicaltrials.gov/study/NCT01948778.

Hemoperfusion is a technique for the extracorporeal elimination of endogenous and exogenous toxins and harmful mediators by adsorption. It can be used as a stand-alone device, as part of a heart-lung machine or extracorporeal membrane oxygenation (ECMO) or, as is currently the case, integrated into a kidney replacement procedure. In the meantime, various suppliers offer devices with different technologies.

The aim of this work was to evaluate the benefits, risks and evidence of the different systems, how they work and for which indications they are approved in Germany.

To achieve this goal, a narrative assessment of the existing literature and guidelines for different indications was performed. The focus was on in vivo studies.

In principle, a distinction must be made in adsorption techniques between pure adsorption and the combination as adsorption and kidney replacement therapy. The adsorbers available in Germany include Cytosorb®, HA-330, Seraph®-100 and Toraymyxin. Combined procedures (adsorption and kidney replacement) are offered with coupled plasma filtration and adsorption (CPFA) and oXiris®. Most adsorbers have been developed for cytokine and endotoxin removal in patients with sepsis; however, to date, no randomized controlled trial (RCT) has demonstrated a survival benefit when using hemoperfusion. Therefore, the S3 guidelines for treatment of sepsis and the surviving sepsis campaign guidelines advise against its routine use. When the corona pandemic began, hemoperfusion was considered as a promising therapeutic approach. Cytosorb®, Seraph®-100, and oXiris® received emergency approval by the FDA to be used in critically ill patients with COVID-19, so questions arose about the appropriateness and importance of its use; however, the data generated did not show positive results, so its use cannot be recommended routinely either. In addition, they are not mentioned as a treatment option in the current guidelines. The use of adsorption procedures in patients with liver failure and rhabdomyolysis has only been rudimentarily studied, so any evidence is currently lacking. The only adsorber that has CE approval in Germany for both applications is Cytosorb®. In the next few years, studies will have to follow that investigate the efficacy and thus either justify or refute the use in clinical routine. Hemoperfusion procedures are used in the heart-lung machine as part of cardiac surgery for either cytokine or anticoagulant adsorption. No congruent data are available to support the use for the elimination of cytokines. If emergency cardiac surgery is required in a patient with pre-existing anticoagulation, hemoperfusion procedures can be used to prevent bleeding complications. Cytosorb® has CE approval for this indication. All available techniques are nonselective adsorption processes, so that adsorption of known and unknown substances can occur. Unintentional adsorption of drugs, such as various anti-infective agents is a relevant risk, especially when used in patients with sepsis.

Various adsorption systems can eliminate different known and unknown substances. Currently, there is a lack of evidence for all indications and systems to justify their routine use except in clinical trials. Future clinical trials should evaluate the potential benefits but also dangers, so that in the meantime the routine use can be justified or a recommendation against the use can be given.

Sepsis leads to organ dysfunction. Acute kidney injury, a common type of organ dysfunction, is associated with a high mortality rate in patients with sepsis. Kidney replacement therapy can correct the metabolic, electrolyte, and fluid imbalances caused by acute kidney injury. While this therapy can improve outcomes, evidence of its beneficial effects is lacking. Herein, we review the indications for blood purification therapy, including kidney replacement therapy, and the current knowledge regarding acute kidney injury in terms of renal and non-renal indications. While renal indications have been well-documented, indications for blood purification therapy in sepsis (non-renal indications) remain controversial. Excessive inflammation is an important factor in the development of sepsis; blood purification therapy has been shown to reduce inflammatory mediators and improve hemodynamic instability. Given the pathophysiology of sepsis, blood purification therapy may decrease mortality rates in these patients. Further trials are needed in order to establish the effectiveness of blood purification therapy for sepsis.

In 2022, we celebrated the 15th anniversary of the University of Alabama at Birmingham (UAB) Continuous Renal Replacement Therapy (CRRT) Academy, a 2-day conference attended yearly by an international audience of over 100 nephrology, critical care, and multidisciplinary trainees and practitioners. This year, we introduce the proceedings of the UAB CRRT Academy, a yearly review of select emerging topics in the field of critical care nephrology that feature prominently in the conference. First, we review the rapidly evolving field of non-invasive hemodynamic monitoring and its potential to guide fluid removal by renal replacement therapy (RRT). We begin by summarizing the accumulating data associating fluid overload with harm in critical illness and the potential for harm from end-organ hypoperfusion caused by excessive fluid removal with RRT, underscoring the importance of accurate, dynamic assessment of volume status. We describe four applications of point-of-care ultrasound used to identify patients in need of urgent fluid removal or likely to tolerate fluid removal: lung ultrasound, inferior vena cava ultrasound, venous excess ultrasonography, and Doppler of the left ventricular outflow track to estimate stroke volume. We briefly introduce other minimally invasive hemodynamic monitoring technologies before concluding that additional prospective data are urgently needed to adapt these technologies to the specific task of fluid removal by RRT and to learn how best to integrate them into practical fluid-management strategies. Second, we focus on the growth of novel extracorporeal blood purification devices, starting with brief reviews of the inflammatory underpinnings of multiorgan dysfunction and the specific applications of pathogen, endotoxin, and/or cytokine removal and immunomodulation. Finally, we review a series of specific adsorptive technologies, several of which have seen substantial clinical use during the COVID-19 pandemic, describing their mechanisms of target removal, the limited existing data supporting their efficacy, ongoing and future studies, and the need for additional prospective trials.

The mortality rate from septic shock in patients with hematological malignancies (HMs) remains significantly higher than that in patients without HMs. A longer resuscitation time would definitely be harmful because of the irreversibly immunocompromised status of the patients. Shortening the resuscitation time through continuous renal replacement therapy (CRRT) with oXiris® would be an attractive strategy in managing such patients.

To explore the effects of CRRT and oXiris® in shortening the resuscitation time and modifying the host response by reducing inflammation mediator levels.

Forty-five patients with HM were diagnosed with septic shock and underwent CRRT between 2018 and 2022. Patients were divided into two groups based on the hemofilter used for CRRT (oXiris® group, n = 26; M150 group, n = 19). We compared the number of days of negative and total fluid balance after 7 d of CRRT between the groups. The heart rate, norepinephrine dose, Sequential Organ Failure Assessment (SOFA) score, and blood lactic acid levels at different time points in the two groups were also compared. Blood levels of inflammatory mediators in the 26 patients in the oXiris® group were measured to further infer the possible mechanism.

The average total fluid balance after 7 d of CRRT in the oXiris® group was significantly lower than that of patients in the M150 hemofilter group. The SOFA scores of patients after CRRT with oXiris® therapy were significantly lower than those before treatment on day 1 (d1), d3 and d7 after CRRT; these parameters were also significantly lower than those of the control group on d7. The lac level after oXiris® therapy was significantly lower than that before treatment on d3 and d7 after CRRT. There were no significant differences in the above parameters between the two groups at the other time points. In the oXiris® group, procalcitonin levels decreased on d7, whereas interleukin-6 and tumor necrosis factor levels decreased significantly on d3 and d7 after treatment.

CRRT with oXiris® hemofilter may improve hemodynamics by reducing inflammatory mediators and playing a role in shortening the resuscitation period and decreasing total fluid balance in the resuscitation phases.

Endotoxin adsorption has received extensive attention in the field of blood purification. However, developing highly efficient endotoxin adsorbents with excellent hemocompatibility remains challenging. In this study, we propose a new approach for developing the functional polyethersulfone (PES) membrane to remove endotoxins. First, the PES polymer is grafted with polyethylene glycol methyl acrylate (PEG-MA) in a homogeneous phase system via γ irradiation, and PES-g-PEG can be directly used to prepare the membrane by the phase inversion method. Then, polydopamine (PDA) is coated as an adhesive layer onto a PES-g-PEG membrane in an alkaline aqueous solution, and lysozyme (Lyz) is covalently immobilized with PDA through the Schiff base reaction. Lysozyme acts as an affinity adsorption ligand of endotoxin through charge and hydrophobic action. Our study reveals that the PEG branched chain and the PDA coating on the PES membrane can maintain the secondary structure of lysozyme, and thus, the immobilized Lyz can maintain high activity. The adsorption capacity of endotoxins for the PES-g-PEG/PDA/Lyz membrane is 1.28 EU/mg, with an equilibrium adsorption time of 6 h. Therefore, the PES-g-PEG/PDA/Lyz membrane shows great potential application in the treatment of endotoxemia.

The aim of this study was to assess risk factors of mortality after unplanned surgery following colorectal resection.

All the consecutive patients who underwent colorectal resection between 2011 and 2020 in a French national cohort were retrospectively included. Perioperative data of the index colorectal resection (indication, surgical approach, pathological analysis, postoperative morbidity), and characteristics of unplanned surgery (indication, time to complication, time to surgical redo) were assessed in order to identify predictive factors of mortality.

Among 547 included patients, 54 patients died (10%; 32 men; mean age = 68 ± 18 years, range 34-94 years). Patients who died were significantly older (75 ± 11 vs 66 ± 12 years, p = 0.002), frailer (ASA score 3-4 = 65 vs 25%, p = 0.0001), initially operated through open approach (78 vs 41%, p = 0.0001), and without any anastomosis (17 vs 5%, p = 0.003) than those alive. The presence of colorectal cancer, the time to postoperative complication and the time to unplanned surgery were not significantly associated to the postoperative mortality. After multivariate analysis, 5 independent predictive factors of mortality were identified: old age (OR 1.038; IC 95% 1.006-1.072; p = 0.02), ASA score = 3 (OR 5.9, CI95% 1.2-28.5, p = 0.03), ASA score = 4 (OR 9.6; IC95% 1.5-63; p = 0.02), open approach for the index surgery (OR 2.7; IC95% 1.3-5.7; p = 0.01), and delayed management (OR 2.6; IC95% 1.3-5.3; p = 0.009).

After unplanned surgery following colorectal surgery, one out of 10 patients dies. The laparoscopic approach during the index surgery is associated with a good prognosis in the case of unplanned surgery.

This study investigates the impact of sequential extracorporeal treatments with oXiris® or CytoSorb® plus Seraph-100® on the clinical and laboratory parameters of critically ill COVID-19 patients with bacterial superinfection.

Patients admitted to the intensive care unit with COVID-19, bacterial superinfection, and undergoing blood purification (BP) were enrolled in this prospective, single-center, observational study. "standard BP" with oXiris® or CytoSorb® were used in 35 COVID-19 patients with bacterial infection. Seraph-100® was added in 33 patients when available serially in the same oXiris® circuit or as sequential treatment with CytoSorb® as a sequential BP.

A significant reduction in SOFA score 3 days after treatment was observed in patients undergoing sequential BP (11.3 vs. 8.17, p < 0.01) compared to those undergoing "standard BP" (11.0 vs. 10.3, p > 0.05). The difference between the observed and expected mortality rate based on APACHE IV was greater in the sequential BP group (42.4% vs. 81.7%, p < 0.001) than the "standard BP" (74.2% vs. 81.7%, p > 0.05). Patients treated with sequential BP had a longer survival than those treated with "standard BP" (22.4 vs. 18.7 months; p < 0.001).

The sequential approach may enhance the positive effect of BP on organ dysfunction among critically ill patients with COVID-19 and bacterial superinfection.

The oXiris is a novel filter for continuous renal replacement therapy (CRRT) featuring an adsorption coating to adsorb endotoxins and remove inflammatory mediators. Given that no consensus has been reached on its potential benefits in treating sepsis, a meta-analysis was conducted to assess its impact on the clinical outcomes of this patient population.

Eleven databases were retrieved to find relevant observational studies and randomized controlled trials. The Newcastle-Ottawa Scale and the Cochrane Risk of Bias Tool were used to assess the quality of the included studies. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) process was employed to assess the certainty of evidence. The 28-day mortality was the primary outcome. Secondary outcomes were 7-, 14-, and 90-day mortality, length of intensive care unit (ICU) and hospital stay, ICU and hospital mortality, norepinephrine (NE) dose, interleukin-6 (IL-6) and lactate levels, and Sequential Organ Failure Assessment (SOFA) score.

The meta-analysis, pooling data from 14 studies, involving 695 patients, showed significant reductions in 28-day mortality [odds ratio (OR) 0.53; 95% confidence interval (CI) 0.36-0.77, p = 0.001] and length of ICU stay [weighted mean difference (WMD) - 1.91; 95% CI - 2.56 to - 1.26, p < 0.001)] in patients with sepsis using the oXiris filter compared to other filters. Besides, the SOFA score, NE dose, IL-6 and lactate levels, and 7- and 14-day mortalities were lower in the oXiris group. However, the 90-day mortality, ICU and hospital mortality, and length of hospital stay were comparable. The quality assessment of the ten observational studies indicated intermediate to high quality (average Newcastle-Ottawa score: 7.8). However, all four randomized controlled trials (RCTs) had an unclear risk of bias. The evidence for all outcomes had a low or very low level of certainty because the original study design was mainly observational studies and the RCTs included had an unclear risk of bias and a small sample size.

The treatment with the oXiris filter during CRRT in sepsis patients may be associated with lower 28-, 7-, and 14-day mortalities, lactate levels, SOFA score, NE dose, and shorter length of ICU stay. However, due to the low or very low quality of evidence, the effectiveness of oXiris filters was still uncertain. Besides, no significant difference was observed for the 90-day mortality, ICU and hospital mortality, and length of hospital stay.

Even in the absence of strong indications deriving from clinical studies, the removal of mediators is increasingly used in septic shock and in other clinical conditions characterized by a hyperinflammatory response. Despite the different underlying mechanisms of action, they are collectively indicated as blood purification techniques. Their main categories include blood- and plasma processing procedures, which can run in a stand-alone mode or, more commonly, in association with a renal replacement treatment. The different techniques and principles of function, the clinical evidence derived from multiple clinical investigations, and the possible side effects are reviewed and discussed along with the persisting uncertainties about their precise role in the therapeutic armamentarium of these syndromes.

Sepsis and septic shock remain drivers for morbidity and mortality in critical illness. The clinical picture of patients presenting with these syndromes evolves rapidly and may be characterised by: (a) microbial host invasion, (b) establishment of an infection focus, (c) opsonisation of bacterial products (e.g. lipopolysaccharide), (d) recognition of pathogens resulting in an immune response, (e) cellular and humoral effects of circulating pathogen and pathogen products, (f) immunodysregulation and endocrine effects of cytokines, (g) endothelial and organ damage, and (h) organ crosstalk and multiple organ dysfunction. Each step may be a potential target for a specific therapeutic approach. At various stages, extracorporeal therapies may target circulating molecules for removal. In sequence, we could consider: (a) pathogen removal from the circulation with affinity binders and cartridges (specific), (b) circulating endotoxin removal by haemoperfusion with polymyxin B adsorbers (specific), (c) cytokine removal by haemoperfusion with sorbent cartridges or adsorbing membranes (non-specific), (d) extracorporeal organ support with different techniques for respiratory and cardiac support (CO₂ removal or extracorporeal membrane oxygenation), and renal support (haemofiltration, haemodialysis, or ultrafiltration). The sequence of events and the use of different techniques at different points for specific targets will likely require trials with endpoints other than mortality. Instead, the primary objectives should be to achieve the desired action by using extracorporeal therapy at a specific point.

Lipopolysaccharide (LPS) or endotoxin, the major cell wall component of Gram-negative bacteria, plays a pivotal role in the pathogenesis of sepsis. It is able to activate the host defense system through interaction with Toll-like receptor 4, thus triggering pro-inflammatory mechanisms. A large amount of LPS induces inappropriate activation of the immune system, triggering an exaggerated inflammatory response and consequent extensive organ injury, providing the basis of sepsis damage. In this review, we will briefly describe endotoxin's molecular structure and its main pathogenetic action during sepsis. In addition, we will summarize the main different available methods for endotoxin detection with a special focus on the wider spectrum offered by omics technologies (genomics, transcriptomics, proteomics, and metabolomics) and promising applications of these in the identification of specific biomarkers for sepsis.

Critically ill patients with sepsis and severe COVID-19 are commonly characterized by a dysregulated immune response and an acute kidney injury. Continuous renal replacement therapy (CRRT) is now proposed as a promising adjuvant therapy to treat these critically ill patients by removing cytokines, pathogen-associated molecular patterns, and damage-associated molecular patterns from the blood. Although multiple hemofilters, including high-cutoff membranes, the oXiris hemofilter, the CytoSorb hemoadsorption device, and the Toraymyxin hemoperfusion cartridge, have been used in current clinical practice, the use of the oXiris hemofilter in critically ill patients is of particular interest because it is the only kind of hemofilter that can provide renal replacement therapy, remove endotoxins, and adsorb cytokines simultaneously. During the past five years, a growing body of literature has shown that CRRT with the oXiris hemofilter can improve hemodynamics and organ function and can decrease cytokines and endotoxins in both septic and COVID-19 patients. Here, we performed a narrative review to describe the development history of the oXiris hemofilter and to discuss the therapeutic effect of oXiris-CRRT on critically ill patients by searching the PubMed, Web of Science, and clinicaltrials.gov databases for articles published from inception to 8 September 2022 (updated on 1 November) with an English language restriction. We also summarized the current knowledge on anticoagulation techniques and safety concerns when delivering oXiris-CRRT sessions.

Critical illness is often complicated by acute kidney injury (AKI). In patients with severe AKI, renal replacement therapy (RRT) is deployed to address metabolic dysfunction and volume excess until kidney function recovers. This review is intended to provide a comprehensive update on key aspects of RRT prescription and delivery to critically ill patients. Recently completed trials have enhanced the evidence base regarding several RRT practices, most notably the timing of RRT initiation and anticoagulation for continuous therapies. Better evidence is still needed to clarify several aspects of care including optimal targets for ultrafiltration and effective strategies for RRT weaning and discontinuation.

oXiris is a new, high-adsorption membrane filter in continuous hemofiltration adsorption to reduce the inflammatory response in sepsis. The investigators retrospectively reviewed patients with sepsis/septic shock who underwent at least one oXiris-treatment from November 2020 to March 2022. The demographic data, baseline levels before treatment, clinical datas, prognosis, and the occurrence of adverse events during treatment were recorded. 90 patients were enrolled in this study. The hemodynamic indices, sequential organ failure assessment score, lactate, inflammatory biomarkers levels were significantly improved at 12 h and 24 h after treatment. Procalcitonin and interleukin-6 reduction post-treatment of oXiris were most pronounced in infection from skin and soft tissue, urinary and abdominal cavity. Logistic regression analysis showed that pre-treatment sequential organ failure assessment score (p = 0.034), percentage decrease in sequential organ failure assessment score (p = 0.004), and age (p = 0.011) were independent risk factors for intensive care unit mortality. In conclusion, oXiris-continuous hemofiltration adsorption may improve hemodynamic indicators, reduce the use of vasoactive drugs, reduce lactate level and infection indicators. Of note, oXiris improve organ function in sepsis, which may result to higher survival rate.