Fractionated plasma separation and adsorption integrated with continuous veno-venous hemofiltration in patients with acute bipyridine herbicide poisoning.

OBJECTIVE: To evaluate the clinical efficacy and safety of fractionated plasma separation and adsorption combined with continuous veno-venous hemofiltration (FPSA-CVVH) treatment in patients with acute bipyridine herbicide poisoning. METHODS: A retrospective analysis of 18 patients with acute bipyridine herbicide poisoning was conducted, of which 9 patients were poisoned by diquat and 9 patients by paraquat. All patients underwent FPSA-CVVH treatment. The serum cytokine levels in pesticide-poisoned patients were assessed. The efficacy of FPSA-CVVH in eliminating cytokines, the 90-d survival rate of poisoned patients, and adverse reactions to the treatment were observed. RESULTS: Fourteen patients (77.8%) had acute kidney injuries and 10 (55.6%) had acute liver injuries. The serum cytokine levels of high mobility group protein B-1 (HMGB-1), interleukin-6 (IL-6), IL-8, interferon-inducible protein-10 (IP-10), monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein-1ß (MIP-1ß) were significantly elevated. A total of 41 FPSA-CVVH treatment sessions were administered. After a single 8-h FPSA-CVVH treatment, the decreases in HMGB-1, IL-6, IL-8, IP-10, MCP-1, and MIP-1ß were 66.0%, 63.5%, 73.3%, 63.7%, 53.9%, and 54.1%, respectively. During FPSA-CVVH treatment, one patient required a filter change due to coagulation in the plasma component separator, and one experienced a bleeding adverse reaction. The 90-d patient survival rate was 50%, with 4 patients with diquat poisoning and 5 patients with paraquat poisoning, and both liver and kidney functions were restored to normal. CONCLUSION: Cytokine storms may play a significant role in the progression of multiorgan dysfunction in patients with acute bipyridine herbicide poisoning. FPSA-CVVH can effectively reduce cytokine levels, increase the survival rate of patients with acute bipyridine herbicide poisoning, and decrease the incidence of adverse events.

Blood purification therapy in chronic renal failure and its impact on renal index, serological index, and inflammatory factors.

Introduction: This study aimed to explore the clinical effects of blood purification therapy in patients with chronic renal disease, measured by renal function index and inflammation. Methodology: Data were collected from a tertiary care hospital in Pakistan between June 2022 and September 2023. Eighty-four patients undergoing maintenance hemodialysis for chronic renal failure were retrospectively included in this cohort. Results: Age, sex, BMI, course of disease, primary disease, and educational level were not related to the response to blood purification treatment. Blood purification therapy positively affected renal function, serological indices, and inflammatory factors (P<0.05). Conclusion: Blood purification therapy can improve toxin clearance and renal function and reduce inflammation. Therefore, the authors can conclude that this is an effective therapy for our population.

A case of multiorgan failure due to carbamazepine intoxication successfully treated with multimodal blood purification therapy.

Carbamazepine (CBZ) intoxication can occur due to various factors, including drug interactions and over-ingestion. Extracorporeal elimination, particularly through hemodialysis and hemoperfusion, is effective in treating severe carbamazepine intoxication. However, as the effectiveness of various modalities can differ, method selection may be based on a specific clinical situation. A 47-year-old woman who took CBZ for schizophrenia presented to our hospital with episodes of vomiting and consciousness disorder. As the CBZ concentration was > 20 µg/mL, she was admitted to the intensive care unit with a diagnosis of acute CBZ poisoning. She underwent one session of hemoperfusion for 2 h, and her CBZ level decreased from > 20 µg/mL to 6.4 µg/mL. However, she developed acute kidney and liver injuries 2 days after admission and underwent intermittent hemodialysis, plasma exchange, continuous hemodiafiltration (CHDF), and online HDF, depending on her condition. Her general condition improved, and she was transferred to the psychiatric department. To our knowledge, no case reports have described severe acute CBZ poisoning in a patient who developed multiorgan failure to date, which was successfully treated with multimodal blood purification therapy. When treating severe CBZ intoxication, blood purification therapy should be tailored to the changing pathophysiology of the condition.

Outcomes of extracorporeal blood purification with oXiris® membrane in critically ill patients: A systematic review and meta-analysis.

PURPOSE: To evaluate the efficacy of the novel oXiris® membrane in critically ill adult patients. METHODS: We systematically searched MEDLINE, EMBASE, and CENTRAL from inception to 01/06/2023 for relevant randomised controlled trials (RCTs) and non-randomised studies of intervention (NRSI). The primary outcome was overall mortality. Random effect meta-analyses were conducted in RevMan 5.4.1. Study quality was evaluated using Cochrane's risk of bias tool. (PROSPERO: CRD42023389198). RESULTS: Ten studies (2 RCTs and 8 NRSIs) with 481 patients were included. None had low risk of bias. Treatment using oXiris® was associated with reduced overall mortality (RR 0.78, 95%CI 0.62-0.98; p = 0.03; 6 NRSI). One RCT reported 28-day mortality, finding no significant difference between groups. Besides, pooled NRSIs results showed significant reductions in SOFA scores, norepinephrine dosage, and several inflammatory biomarkers (C-reactive protein [CRP], lactate, and interleukin-6 [IL-6]) post oXiris® treatment. However, other clinical outcomes (ICU and hospital length of stay, mechanical ventilation duration) were similar between groups. CONCLUSION: In critically ill patients, the use of oXiris® membrane was associated with reduced overall mortality, norepinephrine dosage, CRP, IL-6, lactate levels, along with improved organ function. However, the certainty of evidence was very low, necessitating high-quality RCTs to further evaluate its efficacy in this population.

Capnocytophaga canimorsus Meningitis Complicated by Septic Shock: The Use of Extracorporeal Blood Purification Techniques.

Capnocytophaga canimorsus is a Gram-negative bacterium, commonly found as a commensal germ in the oral cavity of dogs and cats. It is an opportunistic pathogen, but, in specific situations, it can cause very severe diseases, including arthritis, pleuritis, endocarditis, sepsis, and, in extremely rare cases, meningoencephalitis. The predisposing situations include immunosuppression, liver cirrhosis, splenectomy, hemochromatosis, beta thalassemia major (Cooley's anemia), and alcohol abuse. In this report, we describe the case of a 48-year-old male patient, with a medical history of several predisposing conditions, who developed a severe case of meningoencephalitis caused by C. canimorsus, following a dog bite on his hand. The patient was successfully treated for his meningitis, but subsequently he developed a hospital-acquired septic shock from Acinetobacter baumannii, which was treated with targeted antibiotic therapy and sequential extracorporeal blood purification therapies using Oxiris™ and Toraymyxin™ hemofilters.

Evaluation of continuous blood purification in patients with urosepsis caused by ureteral calculi and heart failure after catheterization.

Objective: To detect the continuous blood purification (CBP)'s application value in patients with urosepsis caused by ureteral calculi and heart failure after catheterization. Methods: This is a clinical comparative study. Sixty patients with ureteral calculi complicated with heart failure and urosepsis were admitted at Affiliated Hospital of Hebei University from January 2021 to March 2023 randomly split into control and experimental group(n=30). Based on conventional treatment after indwelling the DJ tube, the experimental group was treated with CBP therapy. The control group dealt with conventional anti-inflammatory, oxygen inhalation and other treatments only. Compared and analyzed in terms of alterations in blood inflammatory factors, cardiac function, BNP prior to and after therapy, blood pressure, blood WBC recovery time, and so on. Results: TNF-a, CRP, and PCT levels in the control and experimental groups were substantially more prominent than the average reference value prior to treatment. They decreased considerably at distinct time points after therapy, with substantial distinctions (p< 0.05). A more meaningful decrease was noticed in the experimental group in comparison with the control group (p< 0.05). BNP and cardiac function were improved in both groups prior to and after therapy, and the amelioration of indexes in the experimental group was more substantial than that in the control group after therapy, with statistically considerable distinctions. The improvement time in experimental group was earlier than in the control group, with statistically substantial differences. Conclusion: Patients with urosepsis complicated with heart failure after indwelling DJ tube have their inflammatory factors improved significantly, with more thorough excretion by using conventional treatment combined with CBP therapy.

A rare case of extensive hydrofluoric acid burn.

Hydrofluoric acid (HF) is a strongly corrosive, highly toxic, and highly dangerous mineral acid. Burns with over 1% total body surface area (TBSA) caused by anhydrous HF can lead to deep tissue damage, hypocalcaemia, poisoning, even death. In recent years, HF has become one of the most common substances causing chemical burns and ranks as the leading cause of death from chemical burns. Herein, we report a rare case with 91% TBSA burns caused by 35% HF. The patient developed complications such as shock, severe hypocalcaemia, metabolic acidosis, and respiratory failure. Multidisciplinary team consultation (burns, respiratory medicine, nephrology, infectious disease, and pharmacy) was performed immediately after admission. An individualized diagnosis and treatment plan was developed for the patient. The patient was given intensive care, blood volume monitoring, tracheotomy, fluid resuscitation, continuous blood purification, anti-infective and analgesic treatments, intravenous and percutaneous calcium supplementation, early rehabilitation training, psychological rehabilitation and other treatments. To prevent the wound from deepening, large-area debridement and skin grafting were performed early after injury. A large dose of 10% calcium gluconate was injected into the patient in divided doses, and the wound was continuously treated with wet dressings. Multiple surgical debridements, negative pressure wound treatment, biological dressings, and Meek skin grafting were performed. After most of the wounds (approximately 85% TBSA) healed, the patient was discharged from the hospital and continued to undergo dressing changes at a local hospital. The patient was followed up 3 months after discharge. All the wounds healed well, and the patient basically regained functional independence in daily life.

Extracorporeal organ support for critically ill patients: Overcoming the past, achieving the maximum at present, and redefining the future.

Extracorporeal organ support (ECOS) has made remarkable progress over the last few years. Renal replacement therapy, introduced a few decades ago, was the first available application of ECOS. The subsequent evolution of ECOS enabled the enhanced support to many other organs, including the heart [veno-arterial extracorporeal membrane oxygenation (ECMO), slow continuous ultrafiltration], the lungs (veno-venous ECMO, extracorporeal carbon dioxide removal), and the liver (blood purification techniques for the detoxification of liver toxins). Moreover, additional indications of these methods, including the suppression of excessive inflammatory response occurring in severe disorders such as sepsis, coronavirus disease 2019, pancreatitis, and trauma (blood purification techniques for the removal of exotoxins, endotoxins, or cytokines), have arisen. Multiple organ support therapy is crucial since a vast majority of critically ill patients present not with a single but with multiple organ failure (MOF), whereas, traditional therapeutic approaches (mechanical ventilation for acute respiratory failure, antibiotics for sepsis, and inotropes for cardiac dysfunction) have reached the maximum efficacy and cannot be improved further. However, several issues remain to be clarified, such as the complexity and cost of ECOS systems, standardization of indications, therapeutic protocols and initiation time, choice of the patients who will benefit most from these interventions, while evidence from randomized controlled trials supporting their use is still limited. Nevertheless, these methods are currently a part of routine clinical practice in intensive care units. This editorial presents the past, present, and future considerations, as well as perspectives regarding these therapies. Our better understanding of these methods, the pathophysiology of MOF, the crosstalk between native organs resulting in MOF, and the crosstalk between native organs and artificial organ support systems when applied sequentially or simultaneously, will lead to the multiplication of their effects and the minimization of complications arising from their use.

[Two cases of pyridaben poisoning were successfully treated by blood purification].

Pyridaben is a broad-spectrum acaricide widely used in agriculture, accidental or self-administration of large doses of pyridaben can cause multiple organ failure in patients. Due to its damage to multiple organs and no specific antidote, the mortality rate is high. This paper reports two patients who took a large amount of pyridaben, developed severe metabolic acidosis, hyperlactatemia, toxic encephalopathy, and liver, kidney, heart and digestive tract damage. After timely gastric lavage, catharsis, organ support andblood purification treatment, the condition improved and discharged. It is expected to provide clinical ideas for the treatment of pyridaben poisoning.

An Evolutionary Review of Hemoperfusion Adsorbents: Materials, Preparation, Functionalization, and Outlook.

Accumulation of pathogenic factors in the blood may cause irreversible damage and may even be life-threatening. Hemoperfusion is an effective technique for eliminating pathogenic factors, which is widely used in the treatment of various diseases including liver failure, renal failure, sepsis, and others. Hemoperfusion adsorbents are crucial in this process as they specifically bind and remove the target pathogenic factors. This review describes the development of hemoperfusion adsorbents, detailing the different properties exhibited by inorganic materials, organic polymers, and new materials. Advances in natural and synthetic polymers and novel materials manufacturing techniques have driven the expansion of hemoperfusion adsorbents in clinical applications. Stimuli-responsive (smart responsive) adsorbents with controllable molecular binding properties have many promising and environmentally friendly biomedical applications. Knowledge gaps, future research directions, and prospects for hemoperfusion adsorbents are discussed.

Application of Nanoparticles as Novel Adsorbents in Blood Purification Strategies.

BACKGROUND: Blood purification therapy for patients overloaded with metabolic toxins or drugs still needs improvement. Blood purification therapies, such as in hemodialysis or peritoneal dialysis can profit from a combined application with nanoparticles. SUMMARY: In this review, the published literature is analyzed with respect to nanomaterials that have been customized and functionalized as nano-adsorbents during blood purification therapy. Liposomes possess a distinct combined structure composed of a hydrophobic lipid bilayer and a hydrophilic core. The liposomes which have enzymes in their aqueous core or obtain specific surface modifications of the lipid bilayer can offer appreciated advantages. Preclinical and clinical experiments with such modified liposomes show that they are highly efficient and generally safe. They may serve as indirect and direct adsorption materials both in hemodialysis and peritoneal dialysis treatment for patients with renal or hepatic failure. Apart from dialysis, nanoparticles made of specially designed metal and activated carbon have also been utilized to enhance the removal of solutes during hemoadsorption. Results are a superior adsorption capacity and good hemocompatibility shown during the treatment of patients with toxication or end-stage renal disease. In summary, nanomaterials are promising tools for improving the treatment efficacy of organ failure or toxication. KEY MESSAGES: (i) The pH-transmembrane liposomes and enzyme-loaded liposomes are two representatives of liposomes with modified aqueous inner core which have been put into practice in dialysis. (ii) Unmodified or physiochemically modified liposomal bilayers are ideal binders for lipophilic protein-bound uremic toxins or cholestatic solutes, thus liposome-supported dialysis could become the next-generation hemodialysis treatment of artificial liver support system. (iii) Novel nano-based sorbents featuring large surface area, high adsorption capacity and decent biocompatibility have shown promise in the treatment of uremia, hyperbilirubinemia, intoxication, and sepsis. (vi) A major challenge of production lies in avoiding changes in physical and chemical properties induced by manufacturing and sterilizing procedures.

The role of hemoadsorption in cardiac surgery - a systematic review.

BACKGROUND: Extracorporeal blood purification has been widely used in intensive care medicine, nephrology, toxicology, and other fields. During the last decade, with the emergence of new adsorptive blood purification devices, hemoadsorption has been increasingly applied during CPB in cardiac surgery, for patients at different inflammatory risks, or for postoperative complications. Clinical evidence so far has not provided definite answers concerning this adjunctive treatment. The current systematic review aimed to critically assess the role of perioperative hemoadsorption in cardiac surgery, by summarizing the current knowledge in this clinical setting. METHODS: A literature search of PubMed, Cochrane library, and the database provided by CytoSorbents was conducted on June 1st, 2023. The search terms were chosen by applying neutral search keywords to perform a non-biased systematic search, including language variations of terms "cardiac surgery" and "hemoadsorption". The screening and selection process followed scientific principles (PRISMA statement). Abstracts were considered for inclusion if they were written in English and published within the last ten years. Publications were eligible for assessment if reporting on original data from any type of study (excluding case reports) in which a hemoadsorption device was investigated during or after cardiac surgery. Results were summarized according to sub-fields and presented in a tabular view. RESULTS: The search resulted in 29 publications with a total of 1,057 patients who were treated with hemoadsorption and 988 control patients. Articles were grouped and descriptively analyzed due to the remarkable variability in study designs, however, all reported exclusively on CytoSorb® therapy. A total of 62% (18/29) of the included articles reported on safety and no unanticipated adverse events have been observed. The most frequently reported clinical outcome associated with hemoadsorption was reduced vasopressor demand resulting in better hemodynamic stability. CONCLUSIONS: The role of hemoadsorption in cardiac surgery seems to be justified in selected high-risk cases in infective endocarditis, aortic surgery, heart transplantation, and emergency surgery in patients under antithrombotic therapy, as well as in those who develop a dysregulated inflammatory response, vasoplegia, or septic shock postoperatively. Future large randomized controlled trials are needed to better define proper patient selection, dosing, and timing of the therapy.

Survival benefit of resin cartridge extracorporeal blood purification therapy in patients with septic shock.

Background/aim: Extracorporeal blood purification (EBP) therapies have shown promise as potential rescue treatments for patients with septic shock. However, precise evidence regarding their effectiveness is lacking. This case-control study aimed to evaluate the 28-day survival benefit of a resin cartridge-based EBP therapy compared to conventional therapies in patients with septic shock. Materials and methods: The study sample was collected retrospectively from the medical records of patients admitted to the intensive care unit (ICU) between 2015 and 2020. The study included patients with septic shock aged ≥18 years who had ICU stays >96 h and excluded those lost to follow-up by 28 days or readmitted. First, 28-day survival was compared between EBP patients and 1:1 matched conventionally treated controls. Second, the EBP patients were evaluated for clinical and laboratory improvements within 72 h of EBP therapy. Results: Of 3742 patients, 391 were included in this study, of whom 129 received EBP therapy and had a 28-day survival rate of 44%, compared to 262 matched controls who received conventional therapy alone and had a survival rate of 33% (p = 0.001, log-rank = 0.05, number needed to treat = 8, and odds ratio = 1.7). After receiving EBP therapy for 72 h, improvements were observed in the Sequential Organ Failure Assessment scores (p < 0.05), shock indices (p < 0.05), partial pressure of oxygen in the arterial blood to the fraction of inspiratory oxygen concentration ratios (p < 0.001), vasopressor requirements (p < 0.001), pH (p < 0.05), lactate levels (p < 0.001), and C-reactive protein levels (p < 0.05). Conclusion: The findings suggest that administering resin cartridge-based EBP therapy to patients with septic shock may improve their survival compared to conventional therapies.

Adjunctive immunotherapeutic agents in patients with sepsis and septic shock: a multidisciplinary consensus of 23.

BACKGROUND: In the last decades, several adjunctive treatments have been proposed to reduce mortality in septic shock patients. Unfortunately, mortality due to sepsis and septic shock remains elevated and NO trials evaluating adjunctive therapies were able to demonstrate any clear benefit. In light of the lack of evidence and conflicting results from previous studies, in this multidisciplinary consensus, the authors considered the rational, recent investigations and potential clinical benefits of targeted adjunctive therapies. METHODS: A panel of multidisciplinary experts defined clinical phenotypes, treatments and outcomes of greater interest in the field of adjunctive therapies for sepsis and septic shock. After an extensive systematic literature review, the appropriateness of each treatment for each clinical phenotype was determined using the modified RAND/UCLA appropriateness method. RESULTS: The consensus identified two distinct clinical phenotypes: patients with overwhelming shock and patients with immune paralysis. Six different adjunctive treatments were considered the most frequently used and promising: (i) corticosteroids, (ii) blood purification, (iii) immunoglobulins, (iv) granulocyte/monocyte colony-stimulating factor and (v) specific immune therapy (i.e. interferon-gamma, IL7 and AntiPD1). Agreement was achieved in 70% of the 25 clinical questions. CONCLUSIONS: Although clinical evidence is lacking, adjunctive therapies are often employed in the treatment of sepsis. To address this gap in knowledge, a panel of national experts has provided a structured consensus on the appropriate use of these treatments in clinical practice.

[Clinical analysis of 4 cases of acute nitrite food poisoning].

Nitrite has high toxicity and is commonly found in food poisoning. Poisoned patients may experience cyanosis of the skin and lips, nausea, vomiting, and difficulty breathing or coma may occur in severe cases. Four cases of nitrite poisoning patients who were transferred from primary hospitals to the Third Affiliated Hospital of Gansu University of Chinese Medicine, the First People's Hospital of Baiyin were reported. After symptomatic supportive treatment with special antidote methylene blue, oxygen inhalation, blood purification, etc., the patients recovered and were discharged after 4 days of treatment.

Clostridium perfringens-induced massive hemolysis treatment with blood purification to target toxins: a case report.

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.

Preliminary report of extracorporeal blood purification therapy in patients receiving LVAD: Cytosorb or Jafron HA330.

BACKGROUND: Left ventricular assist device (LVAD) candidates are at increased risk of immune dysregulation and infectious complications. To attenuate the elevated proinflammatory cytokine levels and associated adverse clinical outcomes, it has been postulated that extracorporeal blood purification could improve the overall survival rate and morbidity of patients undergoing LVAD implantation. METHODS: We retrospectively reviewed prospectively collected data of 15 patients who underwent LVAD implantation at our center between January 2021 and March 2022. Of these, 15 (100%) who received HeartMate 3™ (St. Jude Medical, Abbott, MN, USA) device were eligible. Intraoperatively, patients were single randomized 1:1:1 to three groups: group 1, patients who received Cytosorb therapy (n = 5; installed in the CPB circuit); group 2, patients who received Jafron HA330 (n = 5; installed in the CPB circuit); and control group 3, patients who did not receive filter (n = 5; usual care, neither Cytosorb nor Jafron during CPB). Baseline patient characteristics and intraoperative data were compared between the groups. Blood sample analyses were performed to assess the levels of inflammatory markers (IL-1, 6, 8; CRP, Leukocyte, Lactate, PCT, NT-proBNP, TNF-α) in both preoperative and postoperative data. RESULTS: Baseline patient characteristics were similar in all three groups. We found that IL1α; IL 6; IL8; Lactatedehydrogenase, PCT, pro-BNP, CRP; Leukocyte, and TNFα levels significantly increased with LVAD implantation and that neither Cytosorb nor Jafron influenced this response. In-hospital mortality and overall survival during follow-up were similar among the groups. CONCLUSION: Our preliminary results showed that hemoadsorption therapy using Cytosorb or Jafron hemoadsorption (HA) 330 may not be clinically beneficial for patients with advanced heart failure undergoing LVAD implantation. Large prospective studies are needed to evaluate the potential role of HA therapy in improving outcomes in patients undergoing LVAD implantation.

Septic Hyperinflammation-Is There a Role for Extracorporeal Blood Purification Techniques?

This manuscript investigates the role of extracorporeal blood purification techniques in managing septic hyperinflammation, a critical aspect of sepsis characterized by an uncontrolled immune response leading to multiorgan dysfunction. We provide an overview of sepsis, focusing on the dynamics of immune response, the involvement of neutrophils, and the role of the endothelium in the disease's progression. It evaluates the effectiveness of various blood purification methods, including high-cut-off membranes, high-volume hemofiltration, adsorption techniques, and albumin dialysis, in removing cytokines and endotoxin and improving hemodynamic stability. Despite some very promising results, we conclude that the current evidence does not strongly support these techniques in significantly improving survival rates in septic patients, clearly underlining the need for further research.

Biparatopic Nanobody-Based Immunosorbent for the Highly Selective Elimination of Tumor Necrosis Factor-α.

Removing the overexpressed TNF-α by hemoperfusion positively affects clinical treatments for diseases such as autoimmune disease and sepsis. However, clearance ratios of adsorbents targeting TNF-α were limited by the extremely low concentration of TNF-α (mostly <1000 ng/L in sepsis) and hydrophobic interactions. In this work, biparatopic nanobodies (NbC21) with a high affinity of 19.9 pM, which bind to two distinct sites of TNF-α, were constructed as high-affinity ligands for the immunosorbent. The theoretical maximum adsorption capacity estimated from the Langmuir isotherm was up to 18.22 mg/g gel. The prepared immunosorbent (NbC21-sorbent) had an outstanding TNF-α clearance ratio of approximately 96% during the dynamic adsorption test, with a sorbent-to-serum ratio of 1:1000. Additionally, it demonstrated favorable hemocompatibility and a prolonged storage capability. The results indicated that the biparatopic nanobody immunosorbent exhibited significant potential for clinical applications as it met the stringent criteria for both efficacy and safety.

Middle Molecular Uremic Toxin and Blood Purification Therapy.

The purpose of blood purification therapy is to remove uremic toxins, and middle molecules (MMs) are a specific target. An MM is defined as a solute that passes through the glomerulus with a molecular weight in the range of 0.5-58 kDa, and new classifications of "small-middle 0.5-15 kDa," "medium-middle 15-25 kDa," and "large-middle 25-58 kDa" were proposed. In Japan, the removal of α1-microglobulin (αMG) in the large-middle range has been the focus, but a new theory of removal has been developed, emphasizing the antioxidant effect of αMG as a physiological function. Clinical proof of this mechanism will lead to further development of blood purification therapies.