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Background Blood purification through the removal of plasma solutes by adsorption to beads of charcoal or resins contained in a cartridge (hemoperfusion) has a long and imperfect history. Developments in production and coating technology, however, have recently increased the biocompatibility of sorbents and have spurred renewed interest in hemoperfusion. Methods We performed a narrative assessment of the literature with focus on the technology, characteristics, and principles of hemoperfusion. We assessed publications in ex vivo, animal, and human studies. We synthesized such literature in a technical and state-of-the-art summary. Results Early hemoperfusion studies were hampered by bioincompatibility. Recent technology, however, has improved its safety. Hemoperfusion has been used with positive effects in chronic dialysis and chronic liver disease. It has also demonstrated extraction of a variety of toxins and drugs during episodes of overdose. Trials with endotoxin binding polymyxin B have shown mixed results in septic shock and are under active investigation. The role of non-selective hemoperfusion in sepsis or inflammation remains. Although new technologies have made sorbents more biocompatible, the research agenda in the field remains vast. Conclusion New sorbents markedly differ from those used in the past because of greater biocompatibility and safety. Initial studies of novel sorbent-based hemoperfusion show some promise in specific chronic conditions and some acute states. Systematic studies of novel sorbent-based hemoperfusion are now both necessary and justified.

Severe acute kidney injury (AKI), especially when caused or accompanied by sepsis, is associated with prolonged hospitalization, progression to chronic kidney disease (CKD), financial burden, and high mortality rate. Continuous renal replacement therapy (CRRT) is a predominant form of renal replacement therapy (RRT) in the intensive care unit (ICU) due to its accurate volume control, steady acid–base and electrolyte correction, and achievement of hemodynamic stability. This manuscript reviews the different aspects of CRRT prescription in critically ill patients with severe AKI, sepsis, and multiorgan failure in ICU. These include the choice of CRRT versus Intermittent and extended hemodialysis (HD), life of the filter/dialyzer including assessment of filtration fraction, anticoagulation including regional citrate anticoagulation (RCA), prescribed versus delivered CRRT dose, vascular access management, timing of initiation and termination of CRRT, and prescription in AKI/sepsis including adsorptive methods of removing endotoxins and cytokines.

Septic shock can be caused by a variety of mechanisms including direct effects of bacterial toxins such as endotoxin. Annually, approximately 5–7 million patients worldwide develop sepsis with very high endotoxin activity in the blood and more than half die. The term endotoxic septic shock has been used for these patients but it is important to emphasize that endotoxin may be a factor in all forms of septic shock including non-bacterial etiologies like COVID-19 since translocation of bacterial products is a common feature of septic shock. A pattern of organ failure including hepatic dysfunction, acute kidney injury and various forms of endothelial dysfunction ranging from disseminated intravascular coagulation to thrombotic microangiopathy characterize endotoxic septic shock. However, while characteristic, the clinical phenotype is not unique to patients with high endotoxin, and the diagnosis relies on the measurement of endotoxin activity in addition to clinical assessment. Therapies for endotoxic septic shock are limited with immune modulating therapies under investigation and extracorporeal blood purification still controversial in many parts of the world.

Acute kidney injury (formerly known as acute renal failure) is a syndrome characterised by the rapid loss of the kidney's excretory function and is typically diagnosed by the accumulation of end products of nitrogen metabolism (urea and creatinine) or decreased urine output, or both. It is the clinical manifestation of several disorders that affect the kidney acutely. Acute kidney injury is common in hospital patients and very common in critically ill patients. In these patients, it is most often secondary to extrarenal events. How such events cause acute kidney injury is controversial. No specific therapies have emerged that can attenuate acute kidney injury or expedite recovery; thus, treatment is supportive. New diagnostic techniques (eg, renal biomarkers) might help with early diagnosis. Patients are given renal replacement therapy if acute kidney injury is severe and biochemical or volume-related, or if uraemic-toxaemia-related complications are of concern. If patients survive their illness and do not have premorbid chronic kidney disease, they typically recover to dialysis independence. However, evidence suggests that patients who have had acute kidney injury are at increased risk of subsequent chronic kidney disease.

Sepsis is characterized by a dysregulated immune response to infection leading to life-threatening organ dysfunction. Sepsis-induced liver injury is recognized as a powerful independent predictor of mortality in the intensive care unit. During systemic infections, the liver regulates immune defenses via bacterial clearance, production of acute-phase proteins (APPs) and cytokines, and metabolic adaptation to inflammation. Increased levels of inflammatory cytokines and impaired bacterial clearance and disrupted metabolic products can cause gut microbiota dysbiosis and disruption of the intestinal mucosal barrier. Changes in the gut microbiota play crucial roles in liver injury during sepsis. Bacterial translocation and resulting intestinal inflammation lead to a systemic inflammatory response and acute liver injury. The gut-liver crosstalk is a potential target for therapeutic interventions. This review analyzes the underlying mechanisms for the gut-liver crosstalk in sepsis-induced liver injury.

In accordance with previous studies, the beta coronaviruses SARS-CoV and the most recent SARS-CoV-2 use angiotensin-converting enzyme 2 (ACE-2) as receptor to facilitate viral entry into target cells; ACE-2 is also located on the surface of kidney tubular cells, and their infection may worsen the local inflammatory response and consequently the incidence and the duration of AKI episodes [6] (Table 1). All these risk factors added to the increased incidence of AKI in elderly lead to the hypothesis that renal complications are predominant in patients with pre-existing chronic impairment of kidney function that is difficult to evaluate based only on serum creatinine levels, thus claiming for the use of new biomarkers of early kidney injury. [...]determining the risk for developing AKI in SARS-CoV-2 infected patients or progressing to severe AKI requiring renal replacement therapies [8] is an important step for the patient’s prognosis and for early implementation of preventative and protective measures [7, 9]. In this scenario, much attention has focused on novel biomarkers in the last years, particularly on markers of acute tubular stress/damage such as TIMP-2 (tissue inhibitor of metalloproteinase 2) and IGFBP7 (insulin-like growth factor binding protein 7) and their product [TIMP-2]*[IGFBP-7] identified using the NephroCheck Test [10].

Hypertension cure following adrenalectomy in unilateral primary aldosteronism (PA) remains uncertain. Previous meta-analyses have shown highly variable surgical outcomes. Our study aimed to determine the unknown proportion of complete clinical and biochemical success in tertiary and quaternary referral centers. We conducted a systematic review and meta-analysis of studies reporting surgical outcomes of unilateral PA patients within the Surgical Outcome of PRimary Aldosteronism progNostic mOdels (SOPRANO) study. From 27 publications we identified 32 eligible studies, of which 22 were judged to be at low risk of bias. Eighteen were single-center studies, while fourteen were multi-center studies, with patients recruited from 132 referral centers worldwide. Adrenalectomy was performed on 5887 patients, with 4861 (83%) included in the final analysis. The pooled estimates of complete clinical and biochemical success for all studies were 39% (95% CI: 34-44%) and 99% (95% CI: 96-99%), respectively, similar to that found for studies at low risk of bias. Multivariate meta-regression analyses for all studies and low-bias risk studies revealed that BMI (P < 0.01), recruitment time period (P < 0.01), and hypertension duration (P < 0.05) inversely correlated with complete clinical success, while BMI (P < 0.05) and the number of enrolled centers (P < 0.05) inversely correlated with complete biochemical success. In summary, our findings offer robust estimates of complete clinical and biochemical success rates following adrenalectomy for unilateral PA in tertiary and quaternary referral centers and identify new potential effect modifiers that can help clinicians to inform and counsel patients about post-surgery expectations, guaranteeing effective treatment and ultimately enhancing outcomes.

Sepsis is one of the leading causes of morbidity and mortality worldwide. It is characterized by a dysregulated immune response to infections that results in life-threatening organ dysfunction and even death. Bacterial cell wall components (endotoxin or lipopolysaccharide), known as pathogen-associated molecular patterns (PAMPs), as well as damage-associated molecular patterns (DAMPs) released by host injured cells, are well-recognized triggers resulting in the elevation of both pro-inflammatory and anti-inflammatory cytokines. Understanding this complex pathophysiology has led to the development of therapeutic strategies aimed at restoring a balanced immune response by eliminating/deactivating these inflammatory mediators. Different extracorporeal techniques have been studied in recent years in the hope of maximizing the effect of renal replacement therapy in modulating the exaggerated host inflammatory response, including the use of high volume hemofiltration (HVHF), high cut-off (HCO) membranes, adsorption alone, and coupled plasma filtration adsorption (CPFA). These strategies are not widely utilized in practice, depending on resources and local expertise. The literature examining their use in septic patients is growing, but the evidence to support their use at this stage is considered of low level. Our aim is to provide a comprehensive overview of the technical aspects, clinical applications, and associated side effects of these techniques.

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 (CO 2 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. Graphical Abstract

Key Points Resistance and tolerance mechanisms govern the infection response and determine host survival A switch to Warburg metabolism seems to be an important survival strategy in immune cells and possibly in tubular epithelial cells in response to inflammation Reprogramming of metabolic pathways is a key cellular strategy to execute resistance and tolerance protective programmes Early metabolic reprogramming in the response to inflammation is crucial to determine the acute response of the cell, to avoid cell death and to determine the repair phenotype during recovery Understanding of resistance and tolerance mechanisms in sepsis might provide a basis for the development of therapeutic strategies to prevent or reverse organ damage, promote recovery and decrease mortality Decreasing susceptibility to tissue damage — a protective strategy known as tolerance — might be as important as infection resistance in determining outcomes in sepsis. Here, the authors discuss tolerance mechanisms that act in the kidney during sepsis, with a focus on the role of metabolic reprogramming. The host defence against infection is an adaptive response in which several mechanisms are deployed to decrease the pathogen load, limit tissue injury and restore homeostasis. In the past few years new evidence has suggested that the ability of the immune system to limit the microbial burden — termed resistance — might not be the only defence mechanism. In fact, the capacity of the host to decrease its own susceptibility to inflammation- induced tissue damage — termed tolerance — might be as important as resistance in determining the outcome of the infection. Metabolic adaptations are central to the function of the cellular immune response. Coordinated reprogramming of metabolic signalling enables cells to execute resistance and tolerance pathways, withstand injury, steer tissue repair and promote organ recovery. During sepsis-induced acute kidney injury, early reprogramming of metabolism can determine the extent of organ dysfunction, progression to fibrosis, and the development of chronic kidney disease. Here we discuss the mechanisms of tolerance that act in the kidney during sepsis, with particular attention to the role of metabolic responses in coordinating these adaptive strategies. We suggest a novel conceptual model of the cellular and organic response to sepsis that might lead to new avenues for targeted, organ-protective therapies.