-
American Journal of Physiology. Cell... Jan 2020Extracellular vesicles (EVs) are small lipid membrane vesicles that are secreted from almost all kinds of cells into the extracellular space. EVs are widely accepted to... (Review)
Review
Extracellular vesicles (EVs) are small lipid membrane vesicles that are secreted from almost all kinds of cells into the extracellular space. EVs are widely accepted to be involved in various cellular processes; in particular, EVs derived from cancer cells have been reported to play important roles in modifying the tumor microenvironment and promoting tumor progression. In addition, EVs derived from cancer cells encapsulate various kinds of tumor-specific molecules, such as proteins and RNAs, which contribute to cancer malignancy. Therefore, the unveiling of the precise mechanism of intercellular communication via EVs in cancer patients will provide a novel strategy for cancer treatment. Furthermore, a focus on the contents of EVs could promote the use of EVs in body fluids as clinically useful diagnostic and prognostic biomarkers. In this review, we summarize the current research knowledge on EVs as biomarkers and therapeutic targets and discuss their potential clinical applications.
Topics: Animals; Antineoplastic Agents; Biomarkers, Tumor; Extracellular Vesicles; Gene Expression Regulation, Neoplastic; Hemofiltration; Humans; Molecular Targeted Therapy; Neoplasms; Predictive Value of Tests; Signal Transduction
PubMed: 31693397
DOI: 10.1152/ajpcell.00280.2019 -
Nephrology, Dialysis, Transplantation :... May 2022Haemodiafiltration (HDF) provides a greater removal of larger solutes and protein-bound compounds than conventional high-flux haemodialysis (HD). There are indications...
Haemodiafiltration (HDF) provides a greater removal of larger solutes and protein-bound compounds than conventional high-flux haemodialysis (HD). There are indications that the patients receiving the highest convection volumes of HDF result in improved survival compared with HD. However, the comparative efficacy of HDF versus HD remains unproven. Here we provide a comparative account of the methodology and aims of 'the comparison of high-dose HDF with high-flux HD' (CONVINCE) study in the context of the totality of evidence and how this study will contribute to reaching a higher level of certainty regarding the comparative efficacy of HDF versus HD in people with end-stage kidney disease.
Topics: Convection; Hemodiafiltration; Humans; Kidney Failure, Chronic; Renal Dialysis
PubMed: 35098994
DOI: 10.1093/ndt/gfac019 -
Blood Purification 2019Extracorporeal blood purification is proposed as an adjuvant therapy for sepsis, aiming at controlling the associated dysregulation of the immune system, which is known... (Review)
Review
Extracorporeal blood purification is proposed as an adjuvant therapy for sepsis, aiming at controlling the associated dysregulation of the immune system, which is known to induce organ dysfunctions. Different therapies have been developed to address certain steps of the immune dysregulation. Most of the available blood purification devices focus on a single target, such as the endotoxin that triggers the immune cascade, or the cytokine storm that causes organ damages. However, the highly adsorptive membrane named oXiris® is a unique 4-in-1 device that combines cytokine and endotoxin removal properties, renal replacement function, and antithrombogenic properties. More recently, promising treatments that focus on the pathogen itself or the immune cells have been developed and are currently under investigation. In this review, we aim to summarize, according to their target, the different extracorporeal blood purification techniques that are already available for use. We will also briefly introduce the most recent techniques that are still under development. Because of its unique ability to remove both endotoxins and cytokines, we will particularly discuss the highly adsorptive preheparinized oXiris® membrane. We will present its properties, advantages, pitfalls, as well as therapeutic perspectives based on experimental and clinical data. Video Journal Club "Cappuccino with Claudio Ronco" at https://www.karger.com/Journal/ArticleNews/223997?sponsor=52.
Topics: Cytokines; Endotoxins; Hemofiltration; Humans; Sepsis
PubMed: 30974444
DOI: 10.1159/000499520 -
Journal of the American College of... Sep 2020Acute kidney injury (AKI) and cardiorenal syndrome (CRS) are increasingly prevalent in hospitalized patients with cardiovascular disease and remain associated with poor... (Review)
Review
Acute kidney injury (AKI) and cardiorenal syndrome (CRS) are increasingly prevalent in hospitalized patients with cardiovascular disease and remain associated with poor short- and long-term outcomes. There are no specific therapies to reduce mortality related to either AKI or CRS, apart from supportive care and volume status management. Acute renal replacement therapies (RRTs), including ultrafiltration, intermittent hemodialysis, and continuous RRT are used to manage complications of medically refractory AKI and CRS and may restore normal electrolyte, acid-base, and fluid balance before renal recovery. Patients who require acute RRT have a significant risk of mortality and long-term dialysis dependence, emphasizing the importance of appropriate patient selection. Despite the growing use of RRT in the cardiac intensive care unit, there are few resources for the cardiovascular specialist that integrate the epidemiology, diagnostic workup, and medical management of AKI and CRS with an overview of indications, multidisciplinary team management, and transition off of RRT.
Topics: Acute Kidney Injury; Cardio-Renal Syndrome; Cardiology; Disease Management; Hemofiltration; Humans; Renal Dialysis; Renal Replacement Therapy; Severity of Illness Index; United States; Water-Electrolyte Balance
PubMed: 32854844
DOI: 10.1016/j.jacc.2020.06.070 -
Intensive Care Medicine Sep 2018To identify research priorities in the management, epidemiology, outcome and underlying causes of sepsis and septic shock.
OBJECTIVE
To identify research priorities in the management, epidemiology, outcome and underlying causes of sepsis and septic shock.
DESIGN
A consensus committee of 16 international experts representing the European Society of Intensive Care Medicine and Society of Critical Care Medicine was convened at the annual meetings of both societies. Subgroups had teleconference and electronic-based discussion. The entire committee iteratively developed the entire document and recommendations.
METHODS
Each committee member independently gave their top five priorities for sepsis research. A total of 88 suggestions (ESM 1 - supplemental table 1) were grouped into categories by the committee co-chairs, leading to the formation of seven subgroups: infection, fluids and vasoactive agents, adjunctive therapy, administration/epidemiology, scoring/identification, post-intensive care unit, and basic/translational science. Each subgroup had teleconferences to go over each priority followed by formal voting within each subgroup. The entire committee also voted on top priorities across all subgroups except for basic/translational science.
RESULTS
The Surviving Sepsis Research Committee provides 26 priorities for sepsis and septic shock. Of these, the top six clinical priorities were identified and include the following questions: (1) can targeted/personalized/precision medicine approaches determine which therapies will work for which patients at which times?; (2) what are ideal endpoints for volume resuscitation and how should volume resuscitation be titrated?; (3) should rapid diagnostic tests be implemented in clinical practice?; (4) should empiric antibiotic combination therapy be used in sepsis or septic shock?; (5) what are the predictors of sepsis long-term morbidity and mortality?; and (6) what information identifies organ dysfunction?
CONCLUSIONS
While the Surviving Sepsis Campaign guidelines give multiple recommendations on the treatment of sepsis, significant knowledge gaps remain, both in bedside issues directly applicable to clinicians, as well as understanding the fundamental mechanisms underlying the development and progression of sepsis. The priorities identified represent a roadmap for research in sepsis and septic shock.
Topics: Anti-Bacterial Agents; Antiviral Agents; Delivery of Health Care; Disease Susceptibility; Drug Combinations; Early Diagnosis; Energy Metabolism; Fluid Therapy; Hemofiltration; Humans; Immune Tolerance; Microbiota; Nutritional Support; Plasmapheresis; Point-of-Care Testing; Practice Guidelines as Topic; Precision Medicine; Research; Respiration, Artificial; Resuscitation; Risk Assessment; Sepsis; Shock, Septic; Treatment Outcome; Vasoconstrictor Agents
PubMed: 29971592
DOI: 10.1007/s00134-018-5175-z -
Clinical Journal of the American... May 2021Among its many functions, owing to its oversized effect on colloid oncotic pressure, intravascular albumin helps preserve the effective circulatory volume.... (Review)
Review
Among its many functions, owing to its oversized effect on colloid oncotic pressure, intravascular albumin helps preserve the effective circulatory volume. Hypoalbuminemia is common in hospitalized patients and is found especially frequently in patients who require KRT either for AKI or as maintenance hemodialysis. In such patients, hypoalbuminemia is strongly associated with morbidity, intradialytic hypotension, and mortality. Intravenous albumin may be administered in an effort to prevent or treat hypotension or to augment fluid removal, but this practice is controversial. Theoretically, intravenous albumin administration might prevent or treat hypotension by promoting plasma refilling in response to ultrafiltration. However, clinical trials have demonstrated that albumin administration is not nearly as effective a volume expander as might be assumed according to its oncotic properties. Although intravenous albumin is generally considered to be safe, it is also very expensive. In addition, there are potential risks to using it to prevent or treat intradialytic hypotension. Some recent studies have suggested that hyperoncotic albumin solutions may precipitate or worsen AKI in patients with sepsis or shock; however, the overall evidence supporting this effect is weak. In this review, we explore the theoretical benefits and risks of using intravenous albumin to mitigate intradialytic hypotension and/or enhance ultrafiltration and summarize the current evidence relating to this practice. This includes studies relevant to its use in patients on maintenance hemodialysis and critically ill patients with AKI who require KRT in the intensive care unit. Despite evidence of its frequent use and high costs, at present, there are minimal data that support the routine use of intravenous albumin during KRT. As such, adequately powered trials to evaluate the efficacy of intravenous albumin in this setting are clearly needed.
Topics: Acute Kidney Injury; Albumins; Hemofiltration; Humans; Hypotension; Infusions, Intravenous; Kidney Failure, Chronic; Renal Dialysis
PubMed: 33115729
DOI: 10.2215/CJN.09670620 -
Kidney International Jun 2017Large cohort studies suggest that high convective volumes associated with online hemodiafiltration may reduce the risk of mortality/morbidity compared to optimal... (Comparative Study)
Comparative Study Randomized Controlled Trial
Large cohort studies suggest that high convective volumes associated with online hemodiafiltration may reduce the risk of mortality/morbidity compared to optimal high-flux hemodialysis. By contrast, intradialytic tolerance is not well studied. The aim of the FRENCHIE (French Convective versus Hemodialysis in Elderly) study was to compare high-flux hemodialysis and online hemodiafiltration in terms of intradialytic tolerance. In this prospective, open-label randomized controlled trial, 381 elderly chronic hemodialysis patients (over age 65) were randomly assigned in a one-to-one ratio to either high-flux hemodialysis or online hemodiafiltration. The primary outcome was intradialytic tolerance (day 30-day 120). Secondary outcomes included health-related quality of life, cardiovascular risk biomarkers, morbidity, and mortality. During the observational period for intradialytic tolerance, 85% and 84% of patients in high-flux hemodialysis and online hemodiafiltration arms, respectively, experienced at least one adverse event without significant difference between groups. As exploratory analysis, intradialytic tolerance was also studied, considering the sessions as a statistical unit according to treatment actually received. Over a total of 11,981 sessions, 2,935 were complicated by the occurrence of at least one adverse event, with a significantly lower occurrence in online hemodiafiltration with fewer episodes of intradialytic symptomatic hypotension and muscle cramps. By contrast, health-related quality of life, morbidity, and mortality were not different in both groups. An improvement in the control of metabolic bone disease biomarkers and β2-microglobulin level without change in serum albumin concentration was observed with online hemodiafiltration. Thus, overall outcomes favor online hemodiafiltration over high-flux hemodialysis in the elderly.
Topics: Age Factors; Aged; Aged, 80 and over; Female; France; Geriatric Assessment; Hemodiafiltration; Hospitalization; Humans; Kaplan-Meier Estimate; Kidney; Kidney Diseases; Male; Prospective Studies; Quality of Life; Renal Dialysis; Time Factors; Treatment Outcome
PubMed: 28318624
DOI: 10.1016/j.kint.2017.01.013 -
Blood Purification 2015
Topics: Hemodiafiltration; Humans
PubMed: 26344506
DOI: 10.1159/000437402 -
BMJ Open Feb 2020End-stage kidney disease (ESKD) is a major public health problem affecting more than 2 million people worldwide. It is one of the most severe chronic non-communicable... (Comparative Study)
Comparative Study Randomized Controlled Trial
Benefits and harms of high-dose haemodiafiltration versus high-flux haemodialysis: the comparison of high-dose haemodiafiltration with high-flux haemodialysis (CONVINCE) trial protocol.
INTRODUCTION
End-stage kidney disease (ESKD) is a major public health problem affecting more than 2 million people worldwide. It is one of the most severe chronic non-communicable diseases. Haemodialysis (HD) is the most common therapeutic option but is also associated with a risk of cardiovascular events, hospitalisation and suboptimal quality of life. Over the past decades, haemodiafiltration (HDF) has become available. Although high-dose HDF has shown some promising survival advantage compared to conventional HD, the evidence remains controversial. A Cochrane systematic review found, in low-quality trials, with various convective forms of dialysis, a reduction in cardiovascular, but not all-cause mortality and the effects on non-fatal cardiovascular events and hospitalisation were uncertain. In contrast, an individual patient data analysis suggested that high-dose HDF reduced both all-cause and cardiovascular mortality compared to HD. In view of these discrepant results, a definitive trial is required to determine whether high-dose HDF is preferable to high-flux HD. The comparison of high-dose HDF with high-flux HD (CONVINCE) study will assess the benefits and harms of high-dose HDF versus a conventional high-flux HD in adults with ESKD.
METHODS AND ANALYSIS
This international, prospective, open label, randomised controlled trial aims to recruit 1800 ESKD adults treated with HD in nine European countries. Patients will be randomised 1:1 to high-dose HDF versus continuation of conventional high-flux HD. The primary outcome will be all-cause mortality at 3 years' follow-up. Secondary outcomes will include cause-specific mortality, cardiovascular events, all-cause and infection-related hospitalisations, patient-reported outcomes (eg, health-related quality of life) and cost-effectiveness.
ETHICS AND DISSEMINATION
The CONVINCE study will address the question of benefits and harms of high-dose HDF compared to high-flux HD for kidney replacement therapy in patients with ESKD with a focus on survival, patient perspectives and cost-effectiveness.
TRIAL REGISTRATION NUMBER
Netherlands National Trial Register (NTR 7138).
Topics: Aged; Europe; Female; Follow-Up Studies; Hemodiafiltration; Humans; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Renal Dialysis; Research Design
PubMed: 32029487
DOI: 10.1136/bmjopen-2019-033228 -
Revista Espanola de Quimioterapia :... Oct 2022Sepsis represents a serious risk to the life of any patient, which is why it is crucial to start an effective treatment in all its extremes as soon as possible, that is,... (Review)
Review
Sepsis represents a serious risk to the life of any patient, which is why it is crucial to start an effective treatment in all its extremes as soon as possible, that is, the chosen antibiotics must have activity against the pathogen that produces the condition and, in addition, they must be dosed considering the patient's situation in all its extremes. It should be considered that it will be necessary to adjust the dose when there is edema (drugs with reduced volume of distribution), hypoproteinemia (drugs bound to proteins in a high proportion), obesity, and also when they require the use of external techniques such as ECMO or any of the different types of hemodialysis and hemofiltration.
Topics: Humans; Sepsis; Hemofiltration; Critical Care; Anti-Bacterial Agents; Treatment Outcome
PubMed: 36285854
DOI: 10.37201/req/s03.07.2022