EXTRACORPOREAL BLOOD TREATMENT SYSTEM AND METHOD.

Abstract

The present application relates to an extracorporeal blood treatment system (50) for treating a subject, the system comprising: an extracorporeal blood circuit (52); a dialyzed fluid circuit (54); said extracorporeal blood circuit and the dialyzed fluid circuit are separated by a membrane (56) from a filtration unit (58); at least one blood pump (60) for controlling the flow of blood through the blood circuit; at least one dialyzed fluid pump (68) for controlling the flow of dialyzed fluid through the dialyzed fluid circuit (54); a system computer unit (64) operatively connected to the blood pump and the dialyzed fluid pump, said system computer unit having at least one input means;wherein the system's computer unit is adapted to receive a desired blood concentration GLNb of glutamine, a desired blood concentration GLUCOSAb of glucose, and a desired blood concentration of a ketone body KETONAb; the system's computer unit is adapted to control said blood pump and said dialysate fluid pump so that the actual concentration value GLNa of glutamine is directed to GLNb, the actual concentration value GLUCOSAa of glucose is directed to Db, and the actual concentration value of ketone bodies is directed to KETONAa. The application also relates to a therapeutic assembly for use in the extracorporeal blood therapy system, a method for treating cancer using the system, a controller for controlling the method, and a dialysate suitable for the method. Figure 2 will be published.

Description

EXTRACORPOREAL BLOOD TREATMENT SYSTEM AND METHOD FIELD OF INVENTION This disclosure relates to extracorporeal blood therapy. More specifically, the disclosure relates to the use of extracorporeal blood therapies such as hemodialysis in cancer treatment, systems for such therapies, and user interfaces for monitoring and displaying recorded data (historical data) during such extracorporeal blood therapies. BACKGROUND OF THE INVENTION Most human cancer cells exhibit an altered energy metabolism that distinguishes them from normal cells. Normal cells obtain most of their energy through mitochondrial oxidative phosphorylation, an aerobic process in which glucose is oxidized, first through glycolysis and then through the tricarboxylic acid (TAA) cycle, to produce adenosine triphosphate (ATP). This pathway, in contrast, is only secondary in cancer cells. This was first observed in the 1920s by Warburg. He noted that after cancer cells have metabolized glucose via glycolysis, lactate is produced from puruvate. In normal cells, this occurs only under anaerobic conditions, but in cancer cells, this alternative pathway increases even in the presence of abundant oxygen.This phenomenon was termed “aerobic glycolysis” or the “Warburg effect” (Warburg et al., 1927, Gen Physiol 8: 519-530). The presence of a characteristic glycolytic phenotype in cancer cells was confirmed by subsequent studies that also observed the overexpression of enzymes involved in glycolysis in most cancer cells. The aforementioned metabolic transformation confers a selective growth advantage on cancer cells and contributes to their resistance to hypoxia and apoptosis. Because the proliferation rate of tumor cells exceeds the rate of new blood vessel formation, many tumors grow in a low-oxygen environment. Cancer cells exhibit several metabolic alterations, the most common and well-known being their ability to produce energy through aerobic glycolysis. Furthermore, many glycolytic intermediates, such as ribose, glycerol, and serine, are also intermediates in biosynthetic and anabolic pathways essential for cancer cell growth and proliferation. Additionally, glycolysis produces ATP from ADP, which sustains cell growth within the tumor.However, glycolysis is much less efficient than oxidative phosphorylation, requiring a large amount of glucose to produce sufficient ATP. Therefore, this metabolic pathway is highly glucose-intensive. Many cancer cells become addicted to glucose as their primary energy source. For several reasons, glycolytic tumor cells become vulnerable if their glucose supply is disrupted. Furthermore, many cancer cells also exhibit glutamine addiction. The high rate of glutamine uptake in glutamine-dependent cells is not only due to its role as a nitrogen source in nucleotide and amino acid biosynthesis, but also because glutamine is the primary mitochondrial substrate in cancer and is necessary for producing NADPH for redox control and macromolecular synthesis. Other metabolic alterations in cancers play a significant role in survival, and, importantly, many cancers exhibit a remarkable ability to alter their metabolic profile. This plasticity to withstand environmental challenges, such as reduced glucose, glutamine, or oxygen levels, is crucial for cancer cell survival. Furthermore, many cancer cells also exhibit glutamine dependence. The high rate of glutamine uptake shown by glutamine-dependent cancer cells is not only a result of its role as a nitrogen source for nucleotide and amino acid biosynthesis, but also because glutamine is the primary mitochondrial metabolic substrate in many cancers and is required to produce NADPH for redox control and macromolecular synthesis. There are many metabolic alterations in cancers, and several amino acids, such as glutamine, have important roles in cancer metabolism to control redox balance and produce building blocks for continued proliferation. Furthermore, many cancers exhibit a remarkable ability to utilize these alternative pathways to alter their metabolic profile when necessary to adapt to new metabolic constraints. This ability is a key characteristic of cancers and their capacity to withstand environmental challenges when metabolic energy resources such as glucose, glutamine, or oxygen are scarce. Therefore, to effectively target cancer through a metabolic approach, it's important to affect its metabolic system from more than one angle. While most cancer cells can easily manage glucose reduction, impacting multiple metabolic pathways simultaneously (such as glucose and glutamine reduction) can be far more devastating than the sum of its parts. In addition to glucose, ketones, and glutamine, which are global energy sources for many cancers, serine and glycine satisfy important specific needs for maintaining cell growth and proliferation in cancer, for example, through one-carbon metabolism. Besides a high energy requirement, cancer cells must also accumulate building blocks for constructing new cellular components, including nucleic acids, proteins, and lipids, as well as equally important cofactors for maintaining their cellular redox state (Amelio et al: Trends. Biochem. Sci. (2014), vol. 39(4): 191-198). Studies have shown that arginine is necessary for cell growth and can become limiting in states of rapid growth, and if cancer cells are deprived of it, it also affects survival (Albaugh et al., J.Surg. Oncol. (2017), vol. 115(3), 273-280). In light of the above, it has been suggested that reducing blood glucose levels may serve as a strategy to target a wide range of glycolysis-dependent tumors. Under low-glycemic conditions, fats, and especially ketone bodies, can substitute for glucose as the primary metabolic fuel for normal cells. However, many tumors exhibit abnormalities in the genes and enzymes necessary to metabolize lipids and ketone bodies for energy. Therefore, the transition from carbohydrates to ketones for energy is specifically targeted at the energy metabolism of glycolysis-dependent tumor cells (Seyfried et al., 2010, Nutrition and Metabolism, 7:7). According to this approach, for example, WO2011070527 discloses a method of treating a proliferative disorder, cancerous or non-cancerous, in an individual in whom a hemodialysis machine is used to reduce the concentration of glucose in the blood. The use of a hemodialysis machine to lower blood glucose has the advantage that the blood glucose concentration can be reduced, and therefore lowered, in a more controlled and effective manner compared to glucose deprivation through diet. However, the method and machine disclosed in WO2011070527 require blood glucose and blood glutamine sensors connected to the incoming blood flow, the return blood flow, and the dialysate. These sensors are all connected to the central control unit of the hemodialysis machine. Furthermore, the central control unit of WO2011070527 is also connected to an electroencephalograph (EEG) to provide the central unit with information on spontaneous electrocerebral activity to initiate the increase in glucose and glutamine levels. This large number of sensors and instruments leads to a high level of complexity and associated costs.Furthermore, patients undergoing this treatment must adhere to a glucose-restricted diet for several days before starting the treatment. This is not a negligible burden for the patient. There is a constant need to improve the ways of treating cancer. BRIEF DESCRIPTION OF THE INVENTION In a first aspect of the invention, an extracorporeal blood treatment system (50) is provided for treating a subject suffering from cancer, the system comprising: an extracorporeal blood circuit (52a, 52b); a dialyzed fluid circuit (54a, 54b); said extracorporeal blood circuit (52a, 52b) and the dialyzed fluid circuit (54a, 54b) are separated by a membrane (59) from a filtration unit (58); at least one blood pump (60) to control the flow of blood through the blood circuit (52a, 52b); at least one dialysate fluid pump (62, 68) to control the flow of dialysate fluid through the dialysate fluid circuit (54a, 54b); optionally, one or more infusion lines (66, 80, 81, 82), each infusion line being connected to the extracorporeal blood circuit (52a, 52b) or being adapted to be connected directly to the vascular system of the subject to be treated, each infusion line comprising an infusion pump; a system computing unit (64) operatively connected to the blood pump (60) and the dialysate fluid pump (62, 68) and, optionally, to one or more infusion pumps of one or more infusion lines (66, 80, 81, 82), said system computing unit having a user interface including an input means and a display means; wherein the system computing unit (64) is adapted to receive a desired blood concentration value GLNb of glutamine (901) within the range of 0.1 and 0.5 mM; The system's computer unit (64) is adapted to receive a desired blood concentration value GLUCOSAb of glucose (903) within the range of 2 and 4 mM; The system's computer unit (64) is adapted to receive a desired blood concentration value of a ketone body such as acetoacetate, beta-hydroxybutyrate or pharmaceutically acceptable derivatives, esters and salts thereof (905) within the range of 1 to 15 mM; The system computer unit (64) is adapted to receive a GLNP concentration value representing the concentration of glutamine or pharmaceutically acceptable glutamine-containing compounds in the fresh dialyzer fluid (902); The system's computer unit (64) is adapted to receive a GLUCOSEp concentration value representing the glucose concentration in the fresh dialyzed fluid (904); Optionally, the system computer unit (64) is adapted to receive a KETONAp concentration value, which represents the concentration of a ketone body, such as acetoacetate, beta-hydroxybutyrate or pharmaceutically acceptable derivatives, esters and salts thereof in the fresh dialyzed fluid (907); Optionally, the system computer unit (64) is adapted to receive a KETONE concentration value representing the concentration of a ketone body, such as acetoacetate, beta-hydroxybutyrate or pharmaceutically acceptable derivatives, esters and salts thereof in an infusion fluid to be infused into the extracorporeal bloodline (52b) or directly into the vascular system of the subject to be treated through one of said infusion lines (66, 80, 81, 82) (906); The system computer unit (64) is adapted to receive an actual GLNa concentration value of glutamine (909) in the blood of said treated subject, and to receive an actual blood concentration value of GLUCOSE of glucose (910) in the blood of said treated subject, and to receive an actual concentration value of KETONE of a ketone body such as acetoacetate and beta-hydroxybutyrate (911); The system computer unit (64) is adapted to control said blood pump (60) and said dialysate fluid pump (62, 68) so that the actual blood concentration value GLNa of glutamine is driven to or below GLNb (912) and the actual blood concentration value GLUCOSA of glucose is driven to or below GLUCOSAb (914); and if the system (50) comprises one or more of said infusion lines (66, 80, 81,82) and in the event that one of said infusion lines (66, 80, 81,82) is adapted to infuse said infusion fluid into the extracorporeal blood line (52b) or directly into the vascular system of said subject to treatment, the computer unit of the system (64) is adapted to control said infusion pump of said infusion line so that the actual blood concentration value of KETONAasea is driven towards KETONAAb(920); or alternatively if the system (50) does not comprise said infusion line (66, 80, 81, 82), the system computer unit (64) is adapted to compare KETONEa and KETONEab, and if KETONEa < KETONEab, display a message on said screen informing that the treated subject should consume an additional amount of ketone bodies or medium-chain triglycerides. In this disclosure, the term “subject” refers to a human or animal patient in need of treatment. In a preferred embodiment, the extracorporeal blood treatment system (50) comprises one or more of said infusion lines (66, 80, 81, 82), and the system computer unit (64) is adapted to receive a concentration value, KETONE, representing the concentration of a ketone body such as acetoacetate, beta-hydroxybutyrate, or pharmaceutically acceptable derivatives, esters, and salts thereof in an infusion fluid to be infused into the extracorporeal blood line (52b) or directly into the vascular system of the subject to be treated, through one of said infusion lines (66, 80, 81, 82) (906), and the system computer unit (64) is adapted to control said infusion pump of said infusion line in such a way that the actual blood concentration value of KETONE is fed to KETONE (920). In a preferred embodiment, the system computer unit (64) is adapted to monitor GLNa, and GLUCOSEa, and initiate the infusion of a pharmaceutically acceptable glutamine-containing composition or glutamine-containing compounds if GLNa is less than GLNb (916) and / or initiate the infusion of a glucose-containing composition if GLUCOSEa is less than GLUCOSAb (918) by starting a relevant infusion pump on one or more infusion lines (66, 80, 81, 82), and maintaining such infusion until GLNa is equal to GLNb and GLUCOSEa is equal to GLUCOSAb. The term “pharmaceutically acceptable glutamine-containing compounds” refers to oligopeptides, typically dipeptides in which at least one of the amino acid residues is glutamine. Typical examples of such dipeptides are L-alanyl-L-glutamine and L-glycyl-L-glutamine. Glutamine-containing compounds are often used in place of glutamine in liquid compositions to improve stability and solubility. The term “ketone bodies” refers to water-soluble molecules containing the ketone group that can be produced by the liver from fatty acids. Typically, a ketone body according to the present invention is beta-hydroxybutyrate or a pharmaceutically acceptable derivative thereof, such as its enantiomer (R)-beta-hydroxybutyric acid, (S)-beta-hydroxybutyrate, or an enantiomeric mixture, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable ester thereof, as well as acetoacetate. Medium-chain triglycerides are also considered ketone body derivatives according to the present invention. The term “medium-chain triglycerides” or “MCT oils” refers to triglycerides with two or three fatty acids that have an aliphatic tail of 6 to 12 carbon atoms. These medium-chain triglycerides or MCT oils can be transformed into ketone bodies in the human body.Examples of infusion fluids containing ketone bodies or ketone body derivatives are Lipofundin® MCT / LCT 20% (B. Braun) or SMOFlipid® 20% (Fresenius Kabi). Further examples can be found in WO2018 / 114309 A1. Only the concentration of beta-hydroxybutyrate and / or acetoacetate in a subject's blood is detected as the actual ketone body concentration, since the other ketone body derivatives are transformed into either of these compounds in the subject's body. Preferably, the filtration membrane has a molecular weight cutoff (MWCO) of less than 60 kDa. More preferably, the filtration membrane has an MWCO of less than approximately 50 kDa or less than approximately 40 kDa (e.g., less than 30 kDa, less than 10 kDa, less than 5 kDa or less than 2 kDa). Preferably, the blood circuit comprises a thermal management system to heat or cool the blood in the bloodline during use. More preferably, the thermal management system is controllable to regulate the blood temperature in the blood circuit to a temperature between 20°C and 43°C. Preferably, the system (50) further comprises one or more sensors (S, 90, 91, 92, 93) for the detection of selected analytes from the group of glucose, glutamine and ketone bodies, the sensor(s) (S, 90, 91, 92, 93) being preferably placed in an effluent portion (54a) of the dialyzed fluid circuit, the sensors being in communication with the processing unit of the system (64) and providing an output indicative of the concentration of the analyte(s) in the blood or, preferably, in the spent dialysis fluid; wherein the system processing unit (64) is configured to determine from the output(s) of the sensor(s) (S, 90, 91, 92, 93) a blood concentration representative of the analyte(s), thus controlling at least one, and preferably all of the GLNa, GLUCOSE and KETONE. In a second aspect, the present invention provides a therapeutic assembly for use in an extracorporeal blood treatment system (50) according to the first aspect, comprising a filtration unit (58) having a membrane (59) dividing an integrated blood line (52a, 52b) and an integrated dialysate fluid line (54a, 54b), wherein the blood line (52a, 52b) and / or the dialysate fluid line (54a, 54b) comprises sensors (S, 90, 91, 92, 93) for monitoring at least one of the GLNa, GLUCOSE and KETONE. As shown below, suitable sensors and assays for analyzing glutamine, glucose, and ketone bodies are known in the technique. In a third aspect, the present invention provides a method for treating a subject suffering from cancer using a system (50) comprising: an extracorporeal blood circuit (52a, 52b); a dialyzed fluid circuit (54a, 54b); said extracorporeal blood circuit (52a, 52b) and the dialyzed fluid circuit (54a, 54b) are separated by a membrane (59) from a filtration unit (58); at least one blood pump (60) to control the flow of blood through the blood circuit (52a, 52b); at least one dialysate fluid pump (62, 68) to control the flow of dialysate fluid through the dialysate fluid circuit (54a, 54b); and optionally, one or more infusion lines (66, 80, 81, 82), each infusion line being connected to the extracorporeal circuit (52a, 52b) or adapted to be connected directly to the vascular system of a subject under treatment, each infusion line comprising an infusion pump; where the method comprises: receive a GLNb concentration value that represents a desired blood concentration of glutamine (901) within the range of 0.1 and 0.5 mM; receive a GLUCOSAb concentration value that represents a desired blood glucose concentration (903) within the range of 2 and 4 mM; receive a CETONAb concentration value that represents a desired blood concentration of a ketone body such as acetoacetate, beta-hydroxybutyrate or pharmaceutically acceptable salts, derivatives and esters thereof (905) within the range of 1 and 15 mM; receive a Gl_Np concentration value that represents the concentration of glutamine or pharmaceutically acceptable compounds containing glutamine in the fresh dialyzed fluid (902); receive a GLUCOSAb concentration value that represents the glucose concentration in the dialyzed fluid (904); Optionally, the system computer unit receives a KETONAp concentration value, which represents the concentration of a ketone body, such as acetoacetate, beta-hydroxybutyrate or pharmaceutically acceptable derivatives, esters and salts thereof in the fresh dialyzed fluid (907); Optionally, it receives a KETONE concentration value representing the concentration of a ketone body, such as acetoacetate, beta-hydroxybutyrate or pharmaceutically acceptable derivatives, esters and salts thereof, (906) in an infusion fluid to be infused into the extracorporeal bloodline (52b) or directly into the vascular system of the subject to be treated through one of said infusion lines (66, 80, 81); receives a GLNa concentration value that represents the actual concentration of glutamine in the blood of the treated subject (909); receives a GLUCOSE concentration value that represents the actual concentration of glucose in the blood of the treated subject (910); receives a KETONE concentration value that represents the actual concentration of a ketone body, such as acetoacetate and beta-hydroxybutyrate, in the blood of the treated subject (911); controls said blood pump (60) and said at least one dialysate fluid pump (62, 68) so that the actual concentration value of GLNade glutamine is driven to or below GLNb (912) and the actual concentration value of GLUCOSAade glucose is driven to or below GLUCOSAb (914) and if the system (50) comprises one or more of said infusion lines (66, 80, 81,82) and one of said infusion lines (66, 80, 81,82) infused said infusion fluid into the extracorporeal bloodline (52b) or directly into the vascular system of the subject to be treated, so that CETONAasea was propelled towards CETONAb (920); or, alternatively, if the system (50) does not infuse any infusion fluid containing a ketone body, the subject under treatment is asked to orally consume an amount of ketone bodies or medium-chain triglycerides if the KETONEasea is lower than the KETONEAb. Preferably, said system (50) comprises one or more of said infusion lines (66, 80, 81, 82), and the method further comprises: receive a KETONE concentration value, which represents the concentration of a ketone body such as acetoacetate, beta-hydroxybutyrate or pharmaceutically acceptable derivatives, esters and salts thereof in an infusion fluid (906); infuse said infusion fluid through one of said infusion lines (66,80,81,82) into the extracorporeal blood line (52b) or directly into the vascular system of the subject to be treated; and control the infusion pump of said infusion line so that the actual blood concentration value of KETONAa is directed towards KETONAb (920). Preferably, the cancer is selected from human colon carcinoma and glioblastoma, as well as prostate, breast, and liver cancer. In a fourth aspect, the present invention provides a system computer unit (64) adapted to control an extracorporeal blood treatment system (50) for treating a subject suffering from cancer; said system computer unit comprises: a plurality of output means adapted to be operatively connected to at least one blood pump (60), to at least one dialysate fluid pump (62, 68) and optionally to one or more infusion pumps for controlling the flow in each of one or more infusion lines (66, 80, 81, 82); a user interface that includes an input means and a display means; and a memory means and a calculation means; The system's computer unit (64) is adapted to receive a desired blood concentration value GLNb of glutamine (901); the system's computer unit (64) is adapted to receive a desired blood concentration value GLUCOSAb of glucose (903); The system's computer unit (64) is adapted to receive a desired blood concentration value CETONAb from a ketone body (905); The system's computer unit (64) is adapted to receive a GLNP dialyzed concentration value of glutamine (902); The system's computer unit (64) is adapted to receive a dialyzed concentration value of glucose (904); Optionally, the system computer unit (64) is adapted to receive a KETONAp concentration value, which represents the concentration of a ketone body, such as acetoacetate, beta-hydroxybutyrate or pharmaceutically acceptable derivatives, esters and salts thereof in the fresh dialyzed fluid (907); Optionally, the system computer unit (64) is adapted to receive a KETONE infusion fluid concentration value from a ketone body (906); The system's computer unit (64) is adapted to receive an actual blood concentration value of GLNade glutamine (909); The system's computer unit (64) is adapted to receive an actual blood concentration value GLUCOSE add glucose (910); The system's computer unit (64) is adapted to receive an actual blood concentration value. KETONE adds a ketone body (911) selected from the beta-hydroxybutyrate and acetoacetate group; The system computer unit (64) is adapted to control said blood pump (60) and said dialysate fluid pump (62, 68) so that the actual blood concentration value GLNa of glutamine is driven to or below GLNb (912) and the actual blood concentration value GLUCOSA of glucose is driven to or below GLUCOSAb (914); and in the event that an infusion pump is operatively connected to the system computer unit (64), the system computer unit (64) is adapted to control the infusion pump in such a way that the actual blood concentration value of KETONAasea is driven towards KETONAAb (920); and in the event that no infusion pump is operationally connected to the system computer unit (64), the system computer unit (64) is adapted to compare KETONEa and KETONEAb, and if KETONEa < KETONEAb, display a message on said screen informing that the treated subject should consume an additional amount of ketone bodies or medium-chain triglycerides. In a fifth aspect, the present invention provides a dialysis fluid suitable for the treatment of cancer by dialysis, comprising pharmaceutically acceptable ketone bodies, such as acetoacetate, beta-hydroxybutyrate or derivatives, esters and salts thereof. Preferably, the dialysis fluid also comprises a) glutamine or glutamine-containing compounds; and / or b) glucose. Preferably, the concentration of: a) glutamine or glutamine-containing compounds ranges from 0 to 0.5 mM, and more preferably from 0.05 to 0.3 mM; b) glucose rises from 0 to 6 mM and more preferably from 0.5 to 4 mM; and c) ketone bodies increase from 1 to 15 mM and more preferably from 2 to 12 mM. The foregoing summary of this disclosure is not intended to describe every modality or every implementation thereof. The advantages, along with a more complete understanding of this disclosure, will become apparent and appreciated by referring to the following detailed description and the claims taken in conjunction with the accompanying drawings. BRIEF DESCRIPTION OF THE DRAWINGS FIGURE 1 is a schematic diagram of a system according to the present invention in use. FIGURE 2 is a block diagram of an exemplary extracorporeal blood treatment system that includes an input device and a display device that can utilize the user interfaces and methods described herein. FIGURE 3 is a perspective illustration of an exemplary dialysis system that may include a graphical user interface as described herein. FIGURE 4 is a front view of a portion of the exemplary dialysis system shown in FIGURE 2. FIGURE 5 is a schematic view of a part of a system having thermal management according to an embodiment of the present invention. FIGURE 6A, FIGURE 6B, FIGURE 6C, FIGURE 6D, FIGURE 6E, FIGURE 6F, FIGURE 6G, FIGURE 6H, FIGURE 6I, FIGURE 6J and FIGURE 6K show graphs of the results of study 1. FIGURE 7A, FIGURE 7B, FIGURE 7C and FIGURE 7D, show graphs of the ινΐΛ / a / zuzz / uioi / 1 results of study 2. FIGURE 8A, FIGURE 8B and FIGURE 80 illustrate the treatment objectives according to the present invention. FIG. 9 is a flowchart showing the control algorithm of the present invention. FIGURE 10 shows the growth rate of A549 and RCC4 cells in AC medium as indicated. Figure 11 shows the cell counts of lung carcinoma A549, renal carcinoma RCC4, and primary ROO after 3 days of culture in AC medium at 21% or 5% oxygen. Stars indicate significantly different values ​​determined by two-way ANOVA with Tukey's multiple comparison test. Figure 12 shows the results of culturing the human glioma cell line A172 under normoxia and hypoxia in AC medium with the addition of 8 mM Acac, 16 mM BOHB, or the combination of 4 mM Acac / 8 mM BOHB. 4 and 8 mM LICI are used as controls for Acac. Significantly different values ​​determined by one-way ANOVA with Sidak's multiple comparisons test are marked with stars. Figure 13 illustrates the results of culturing the U118MG glioma cell line under normoxia and hypoxia in AC media with the addition of 8 mM Acac, 16 mM BOHB, or the combination of 4 mM Acac / 8 mM BOHB. 4 and 8 mM LiCI are used as controls for Acac. Significantly different values ​​determined by one-way ANOVA with Sidak's multiple comparisons test are marked with stars. Figure 14 shows the results of culturing the A172 glioma cell line under normoxia and hypoxia in BC medium with the addition of 8 mM Acac, 16 mM BOHB, or the combination of 4 mM Acac and 8 mM BOHB. 4 and 8 mM LiCI are used as controls for the 4 mM Acac / 8 mM BOHB or 8 mM Acac, respectively. Significantly different values ​​determined by one-way ANOVA with Sidak's multiple comparisons test are marked with stars. Figure 15 shows the results of culturing the U118MG glioma cell line under normoxia and hypoxia in BC medium with the addition of 8 mM Acac, 16 mM BOHB, or the combination of 4 mM Acac and 8 mM BOHB. 4 and 8 mM LiCI are used as controls for the 4 mM Acac / 8 mM BOHB or 8 mM Acac, respectively. Significantly different values ​​determined by one-way ANOVA with Sidak's multiple comparisons test are marked with stars. Figure 16 shows the results of culturing the RCC4 renal cell carcinoma cell line under normoxia and hypoxia in BC medium with the addition of 8 mM Acac, 16 mM BOHB, or the combination of 4 mM Acac and 8 mM BOHB. 4 and 8 mM LiCI are used as controls for the 4 mM Acac / 8 mM BOHB or 8 mM Acac, respectively. Significantly different values ​​determined by one-way ANOVA with Sidak's multiple comparisons test are marked with stars. DETAILED DESCRIPTION OF THE INVENTION Exemplary systems and methods for selecting, visualizing, and filtering historical data for extracorporeal blood transfusions will be described with reference to Figure 1, Figure 2, Figure 3, Figure 4, and Figure 5. Extracorporeal blood transfusion systems may record, or store, one or more parameters and / or events from one or more extracorporeal blood transfusions, resulting in historical data. The exemplary systems and methods described herein provide graphical user interfaces for displaying such historical data.Generally, historical data may include patient fluid extraction data, fluid data, treatment data, anticoagulation data, pressure data, event data, configuration data, patient data, alarm data, system voltage and current data, system timing data, user interaction data (e.g., interactions with the user interface, such as button presses and screen selections), etc. In the present invention, the data may include the concentration of certain substances in the patient's bloodstream, as the system may comprise one or more sensors to detect such concentrations. The substances detected may include glucose, glutamine, and other amino acids such as serine, glycine, and arginine, ketones, and cytokines. Patient fluid removal data may include total patient fluid removal data, unintentional patient fluid removal data, selected limits data (e.g., selected limits for unintentional patient fluid gain / loss over a selected period, such as 1 hour, 3 hours, or 24 hours), etc. Fluid data may include pre-infusion data, dialysate data, post-replacement fluid data, filter data, effluent data, filtration fraction data, pre-dilution data, rate data per kilogram of patient, ultrafiltration rate data, post-blood flow rate % ultrafiltration rate data, etc.Treatment data may include prescribed effluent dose data, delivered effluent dose data, target effluent dose data, prescribed ultrafiltration rate (UFR) dose data, target UFR dose data, delivered UFR dose data, etc. Anticoagulation data may include heparin data, estimated patient citrate load data, citrate solution data, calcium solution data, replacement solution data, calcium compensation data, syringe volume delivery data, bolus delivery data, etc.Pressure data may include access line pressure data, return line pressure data, filter pressure data, transmembrane pressure (TMP) data, pressure drop across the filter (P DROP) data (e.g., pressure conditions in the blood compartment of a filter), self-test data, pressure alarm data, disconnect and occlusion limit data, stabilization pressure data, etc. Event data may include system configuration data, alarm data, configuration data, therapy configuration data, counseling data, prescription configuration data, system configuration data, anticoagulation data, pressure data, patient data, mechanical data, dose data, etc. An exemplary extracorporeal blood treatment system 10, as depicted in FIGURE 1, may be used to perform the exemplary methods and / or processes described herein. In at least one embodiment, the system 10 may be or comprise a machine for the extracorporeal treatment of blood. The system 10 could, for example, alternatively be or comprise a blood processing device, a blood component preparation device, or other medical apparatus for the delivery and / or collection of fluids. As shown, the exemplary extracorporeal blood treatment system 10 includes a computer apparatus 12. The computer apparatus 12 can be configured to receive input from the input apparatus 20 and transmit output to the display apparatus 22. In addition, the computer apparatus 12 can include a data storage unit 14. The data storage unit 14 can allow access to processing programs or routines 16 and one or more types of data 18 that can be employed to carry out exemplary methods and / or processes for use in the extracorporeal blood treatment modality, the recording of historical data, the filtering of historical data, and the display of historical data.For example, the computing device 12 may be configured to record, or log, data such as flow rates and volumes, to allow a user to select and view various sets of historical data using the input device 20 (for example, based on user input), and to display the user-selected historical data using the display device 22. The computing device 12 can be operationally coupled to the input device 20 and the display device 22 to, for example, transmit data to and from each of the input devices 20 and the display device 22. For example, the computing device 12 can be electrically coupled to each of the input devices 20 and the display device 22 using, for example, analog electrical connections, digital electrical connections, wireless connections, bus-based connections, etc. As described later, a user can provide inputs to the input device 20 to manipulate, or modify, one or more graphical representations (for example, windows, regions, areas, buttons, icons, etc.) displayed on the display device 22 to select and / or display historical data.Furthermore, various devices and apparatus may be operationally coupled to the computing apparatus 12 for use within the computing apparatus 12 to perform one or more extracorporeal procedures / treatments, as well as the functionality, methods, and / or logic described herein. As shown, the system 10 may include an input apparatus 20 and a display apparatus 22. The input apparatus 20 may include any apparatus capable of providing input to the computing apparatus 12 to perform the functionality, methods, and / or logic described herein. For example, the input apparatus 20 may include a touchscreen (e.g., a capacitive touchscreen, a resistive touchscreen, a multi-touch touchscreen, etc.), a mouse, a keyboard, a trackball (scroll wheel), etc.Input device 20 may allow a user to select and filter various historical data for display on display device 22 (e.g., by displaying a graphical user interface that represents the historical data). Furthermore, the display device 22 may include any device capable of displaying information to a user, such as a graphical user interface, etc., to perform the functionality, methods, and / or logic described herein. For example, the display device 22 may include a liquid crystal display, an organic light-emitting diode display, a touchscreen, a cathode ray tube display, etc. In at least one embodiment, the touchscreen device may be overlaid on a display screen, allowing a user to touch graphical buttons and icons on the display screen to enable specific actions to occur. As described below, the display device 22 can be configured to display a graphical user interface that includes one or more regions and / or areas used to select and display live and / or historical data for extracorporeal blood therapy. For example, the graphical user interface displayed by the display device 22 may include, or display, a two-dimensional graph, data sets plotted on the two-dimensional graph, one or more graphic elements, or icons, representing events adjacent to the two-dimensional graph, a time interval selection region, an event type selection region, an event list region or view, event information areas, a historical data region, an event display region, and so on. Each chart, region, view, button, icon, panel, area, dialog, etc., can be used by a user to select and display historical data in the graphical user interface of the display device. As used herein, a “region” of a graphical user interface can be defined as a portion of the graphical user interface within which information can be displayed or functionality performed. Regions can exist within other regions, can be displayed separately or simultaneously, etc. For example, smaller regions can be located within larger regions, regions can be located next to each other, etc. Furthermore, as used herein, an “area” of a graphical user interface can be defined as a portion of the graphical user interface located within a region that is smaller than the region within which it is located. Processing programs or routines 16 may include programs or routines for performing computational mathematics, matrix mathematics, standardization algorithms, comparison algorithms, or any other processing required to implement one or more of the exemplary methods and / or processes described herein.Data 18 may include, for example, historical data, user accounts, license information, treatment profiles, bitmaps, videos, calibration data, system configuration information, solution data, engineering logs, event and alarm data, system pressures, system voltages, system currents, self-test sequence data, user interaction data, treatment status data, monitor usage data, utilization data, software executables, patient information, treatment summary information, treatment runtime data, graphics (for example, graphic elements, icons, buttons, windows, dialogs, drop-down menus, graphic areas, graphic regions, 3D graphics, etc.).), graphical user interfaces, results of one or more processing programs or routines employed in accordance with the disclosure hereof, or any other data that may be necessary to carry out one and / or more processes or methods described herein. In one or more modes, System 10 can be implemented using one or more computer programs running on programmable computers, such as computers that include, for example, processing capabilities, data storage (e.g., volatile or non-volatile memory and / or storage elements), input devices, and output devices. The program code and / or logic described herein can be applied to the input data to perform the functionality described herein and generate the desired output information. The output information can be applied as input to one or more devices and / or methods as described herein or as would be applied in a known manner. The program used to implement the methods and / or processes described herein may be provided using any programmable language, for example, a high-level procedural and / or object-oriented programming language suitable for communicating with a computer system. Any such program may, for example, be stored on any suitable device, such as a storage medium, that is readable by a general-purpose or special-purpose program running on a computer system (including, for example, a processing unit) to configure and operate the computer system when the suitable device is accessed to perform the procedures described herein.In other words, in at least one embodiment, System 10 can be implemented using a computer-readable storage medium configured with a computer program, where the storage medium so configured causes the computer to operate in a specific and predefined manner to perform the functions described herein. Furthermore, in at least one embodiment, System 10 can be described as implemented by logic (e.g., object code) encoded on one or more non-transient media that include code for execution and, when executed by a processor, is operable to perform operations such as the methods, processes, and / or functionality described herein. Additionally, System 10 may be configured on a remote site (e.g., an application server) that allows access by one or more users through a remote computing device (e.g., through a web browser), and allows a user to employ functionality in accordance with this disclosure (e.g., the user accesses a graphical user interface associated with one or more programs for processing data). Computing Device 12 can be, for example, any fixed or mobile computing system (e.g., a controller, a microcontroller, a personal computer, a minicomputer, etc.). The exact configuration of Computing Device 12 is not limiting, and essentially any device capable of providing adequate computing and control capabilities (e.g., graphics processing, control of extracorporeal blood treatment equipment, etc.) can be used. As described herein, a digital file can be any medium (e.g., volatile or non-volatile memory, a CD-ROM, a punched card, a recordable magnetic tape, etc.) that contains digital bits (e.g., encoded in binary, trinitrate, etc.) that can be read and / or written by the computer apparatus 12 described herein. Furthermore, as described herein, a user-readable file can be any data representation (e.g., ASCII text, binary numbers, hexadecimal numbers, decimal numbers, graphically, etc.) presentable on any medium (e.g., paper, a screen, etc.) readable and / or understandable by a user. In view of the foregoing, it will readily be apparent that the functionality described in one or more modalities in accordance with this disclosure can be implemented in any manner known to a person skilled in the art. As such, the computer language, computer system, or any other software / hardware used to implement the processes described herein will not limit the scope of the systems, processes, or programs (e.g., the functionality provided by such systems, processes, or programs) described herein. It is acknowledged that a graphical user interface may be used in conjunction with the methods described herein. The user interface may provide various features that allow user input, input switching, file import or export, or any other feature that may be generally suitable for use with the processes described herein. For example, the user interface may allow users to select and filter various historical data to be displayed on the display device. The methods and / or logic described in this disclosure, including those attributed to systems or various constituent components, may be implemented, at least in part, in hardware, software, firmware, or any combination thereof. For example, various aspects of the techniques may be implemented within one or more processors, including one or more microprocessors, DSPs, ASICs, FPGAs, or any other equivalent integrated or discrete logic circuit, as well as any combination of such components, or other devices. The term “processor” or “processing circuit” may generally refer to any of the above logic circuits, alone or in combination with other logic circuits, or any other equivalent circuit. The hardware, software, and / or firmware described herein may be implemented within the same device or within separate devices to support the various operations and functions described. Furthermore, any of the described components may be implemented together or separately as discrete logic devices. The representation of different features, for example, by block diagrams, etc., is intended to highlight different functional aspects and does not necessarily imply that such features must be implemented by separate hardware or software components. Rather, the functionality may be implemented by separate hardware or software components, or integrated within common or separate hardware or software components.When implemented in software, the functionality attributed to the systems, devices, and methods described in this disclosure may be incorporated as instructions and / or logic on a computer-readable medium such as RAM, ROM, NVRAM, EEPROM, flash memory, magnetic data storage media, optical data storage media, or similar. The instructions and / or logic may be executed by one or more processors to support one or more aspects of the functionality described in this disclosure. The exemplary systems, and the exemplary methods executed or used by such exemplary systems, described herein for the selection and visualization of historical data in extracorporeal blood treatment may be generally referred to as dialysis systems. The general term dialysis, as used herein, includes hemodialysis, hemofiltration, and hemodiafiltration. In dialysis, blood is generally removed from the body and exposed to a treatment device to separate substances from it and / or add substances to it, and the blood is then returned to the body. Accordingly, extracorporeal blood treatment systems capable of performing general dialysis are described herein with reference to the exemplary extracorporeal blood treatment system in Figure 2, Figure 3, and Figure 4.Other systems may benefit from the systems, methods, and apparatus described herein, and this disclosure is not limited to any particular fluid processing system. In the schematic view of FIGURE 2, the exemplary extracorporeal blood treatment system 50 generally includes a blood tubing circuit 52 comprising an arterial line 52a and a venous line 52b that are connectable to a patient's vascular system. The apparatus comprises a filtration unit 58 having a primary chamber (blood chamber) and a secondary chamber (dialysate chamber) separated by a semipermeable filtration membrane 59. The inlet of the primary chamber is connected to the blood collection line or arterial line 52a. Likewise, the outlet of the primary chamber is connected to the blood return line or venous line 52b. The inlet of the secondary chamber is connected to a fresh dialysis fluid supply line 54b, which in turn is connected to a source 74 to provide fresh dialysis solution. The outlet of the secondary chamber of the filtration unit 58 is connected to a spent dialysis or dialysate line 54a, which carries spent dialysis solution to an effluent connector 73. In the present invention, the filtration unit 58 comprises a membrane 59 that differs from conventional hemodialysis filtration membranes in that it is configured to remove relatively small compounds from the blood in the blood tube circuit 112. The membrane is configured to have a molecular weight cutoff (MWCO) of 50 kDa or less or even 40 kDa or less (such as 30 kDa or less, 10 kDa or less, 5 kDa or less or 2 kDa or less). The flow of blood through blood lines 52a, 52b, and filtration unit 58 is governed by a blood pump 60 located in arterial line 52a. Similarly, the flow of fresh dialysate from source 74 through filtration unit 58 to effluent collector 73 is governed by a dialysate pump 68 in supply line 54b, while the pressure in dialysate line 54 is governed by a pressure relief valve in spent dialysate line 54a. Alternatively, a second pump 62 could be included in spent dialysate line 54a instead of a pressure relief valve. There may also be one or more infusion lines 66, 80, 81, 82 connected to the venous portion of bloodline 52b. In some modalities, one or more of these infusion lines are adapted to be connected directly to a patient's vascular system (not shown in the figures). Each of the infusion lines 66, 80, 81, 82 may comprise separate pumps. In one modality, an infusion fluid containing ketone bodies or ketone body derivatives may be infused through such an infusion line. A system computing unit 64 is provided in communication with the blood pump 60, the dialysate pump 68, and one or more pumps of the one or more infusion lines 66, 80, 81, 82, and the pressure relief valve or additional dialysate pump 68 in order to provide control over these devices in use. In an alternative embodiment, the system computing unit 64 provides the user with appropriate configuration data through a graphical user interface for the pumps of the one or more infusion lines 66, 80, 81, 82. The system computing unit is also in communication with an input medium for supplying information and instructions to the system processing unit 64. The input medium may comprise a graphical user interface, such as one that can be controlled by using a touchscreen. In some embodiments, the input medium may comprise a keyboard.In some modalities, the input means may include one or more sensors to detect the concentration of various substances or conditions in the patient's blood and / or in the spent dialysate. For example, sensors can be provided to detect the concentration of one or more amino acids, such as glutamine, serine, glycine, glucose, arginine, ketones, and cytokines, in the subject's blood. In particular, such sensors must be adapted to detect the concentration of one or more of the glutamine, glucose, and ketone bodies in the subject's blood. Such sensors (S, 91, 93) can be provided in the bloodline (52) or by using separate devices that can be placed elsewhere on the patient's body (S, 90). The sensors, to the extent that they are deployed, provide an indication to the system's processing unit (64) (either directly or via an additional input means) of the actual blood concentration of the intended analyte. This indication can be provided periodically or substantially continuously during treatment. Suitable sensors and assays for analyzing glutamine, glucose, and ketone bodies are known in the art. For example, glutamine sensors are disclosed in US A 4780191. Examples of glutamine assays are disclosed in US 9995750 and US 2016 / 168619. Examples of sensors and assays for determining ketone body concentrations are disclosed in US 8532731 B2, WO 2016 / 178823, US 5326697, and US 5618686. Examples of glucose sensors and assays are described in US 2019 / 328288, US 2018 / 128767, and US 2011 / 105871. Furthermore, the patient's blood concentration of one or more amino acids, such as glutamine, serine, glycine, and arginine, as well as glucose, ketones, and cytokines (preferably at least glucose and glutamine), can be measured by separately extracting and analyzing (e.g., laboratory tests) the patient's blood. This method can be particularly relevant during long-term treatments, although depending on the proximity and speed of the testing facilities, it can be deployed during any treatment. In another embodiment, one or more S,92 sensors may be optionally included in the effluent line 54b. This sensor can detect the concentration of one or more of the following: glucose, amino acids such as glutamine, serine, glycine, and arginine, ketones, or cytokines, as required. The concentration of the relevant analyte measured in the effluent line may be used to determine a representative concentration of the relevant analyte in the patient's blood, as described in European patent EP2377563 (which is incorporated herein by reference). When the body's cells are exposed to higher than normal temperatures, changes occur within them. Treatment can be local (only the tumor), regional (such as a limb), or whole-body hyperthermia, depending on the size of the area being treated. Very high temperatures can cause necrosis / apoptosis of cancer cells (thermal ablation), but high temperatures can also cause injury or induce apoptosis / necrosis in normal cells. Therefore, hyperthermia must be carefully controlled. Hyperthermia is a promising way to improve cancer treatment, but currently requires specialized equipment and is therefore cumbersome to perform. Many clinical trials are underway on hyperthermia for cancer treatment. An extracorporeal circuit, such as the one suggested, is well-suited for both inducing and controlling hypothermia in the patient. Increasing blood temperature simultaneously with the treatment of the extracorporeal blood contents constitutes a good combination therapy that can enhance the effect of the modified blood contents. With a blood flow of 300 mL / min and a returning blood temperature of 43 degrees Celsius, approximately 120 watts of heat effect are transferred to the patient, easily raising their body temperature. The blood temperature could be increased to 45 degrees Celsius for a short period without substantially damaging the blood. Cooling the patient may be necessary to end treatment, but also to modulate an overly effective treatment. Cooling will lead to a reduction in the metabolic rate in both normal and cancerous cells, as well as in their oxygen consumption. These changes will protect healthy cells but weaken cancerous cells against, for example, conventional cancer treatments, as well as cancer dialysis and the reduction of glucose, glutamine, and oxygen. Cooling could also lead to fewer adverse side effects from the conventional cancer treatment administered to the patient, and even to greater resistance to more aggressive cancer dialysis and conventional cancer treatments.The present drawings do not indicate any means of cooling or warming the blood, but such means are well known to the expert and are frequently used in connection with some types of extracorporeal blood therapy, such as continuous renal replacement therapy (CRRT). Figure 8A, Figure 8B, and Figure 80 illustrate the therapeutic aims and principles of the present invention. Each diagram reveals examples of normal conditions with respect to the concentration of a specific blood component. Figure 8A shows that at the start of treatment, the patient typically has an actual blood concentration of glutamine (GLNa) within the range of 0.20 to 0.8 mM. During treatment, the actual blood concentration of glutamine is reduced to a desired value (GLNb), which is within the range of 0.1 to 0.5 mM, and, for example, within the range of 0.15 to 0.3 mM. Figure 8B shows that at the start of treatment, the patient typically has an actual blood concentration of glucose (GLCOSAa) within the range of 4 to 8 mmol / L. During treatment, the actual blood glucose concentration is reduced to a desired value (GLCOSAb), which is typically within the range of 2 to 4 mmol / L.Finally, FIGURE 8C shows that the blood initially contains almost no ketone bodies such as beta-hydroxybutyric acid or a physiologically acceptable salt or ester thereof, such as the sodium salt. Consequently, the actual value of the ketone body concentration in the patient's blood (KETONaa) is approximately 0. Typically, fresh dialysate contains no ketone bodies or only trace amounts. During treatment, the blood concentration of these ketone bodies can be increased to a desired value (KETONAb) within the range of 1 to 15 mmol / L, for example, within the range of 2 to 12 mM, by infusing a ketone body solution and / or ketone body derivatives. In one modality, the actual blood concentration of glutamine, GLNa, and / or the actual blood concentration of glucose, GLCOSAa, could fall below the desired values ​​GLNb and / or GLCOSAb. Therefore, these actual blood concentration values ​​GLNa and / or GLCOSAa could be increased to the desired values ​​GLNb and / or GLCOSAb by infusing solutions containing glucose and / or glutamine or pharmaceutically acceptable glutamine-containing compounds. Figure 9 reveals the flowchart of an example of a 900 algorithm for a control process according to the present invention. Before starting treatment, the system's computer unit 64 is adapted to receive the target treatment concentrations or desired blood concentrations of the key compounds. Typically, these target treatment concentrations are entered via the user interface. Therefore, at step 901, the system 64 computer unit receives a desired blood concentration value of glutamine, GLNb. In step 903, the system 64 computer unit receives a desired blood glucose concentration value, GLUCOSAb. In step 905, the system 64 computer unit receives a desired blood concentration value of ketone bodies, CETONAb. Before treatment begins, the System 64 computer unit is also configured to receive the concentration values ​​in the fresh dialysate for the key components mentioned above. These concentration values ​​are typically also entered via the user interface. Therefore, at stage 902, the system 64 computer unit receives the glutamine concentration value, GLNP, in the fresh dialyzed fluid. In step 904, the computer unit of system 64 receives the glucose concentration value, GLUCOSAP, in the fresh dialyzed fluid. In step 907, the system's computer unit (64) is adapted to receive a CETONAP concentration value, which represents the concentration of a ketone body, such as acetoacetate, beta-hydroxybutyrate or pharmaceutically acceptable derivatives, esters and salts thereof in the fresh dialyzed fluid; In step 906, the computer unit of system 64 receives the value of the concentration of ketone bodies, KETONEj, in an infusion fluid to be infused into the extracorporeal bloodline (52b) or directly into the vascular system of the subject / patient to be treated. Before treatment begins, and optionally during treatment, the system's computer unit 64 is adapted to receive actual concentration values ​​determined from the patient's blood. These concentration values ​​can be obtained after blood sampling and subsequent analysis in separate analysis units. The concentration values ​​are then entered manually via the user interface. In some modalities, the system's computer unit is connected to one or more of these separate analysis units and can therefore receive data directly from them. In some modalities, the blood circuit 52a, 52b, and / or the dialysate circuit 54a, 54b may include suitable sensors S, 90, 91, 92, 93, which are connected to the system's computer unit 64 that receives the data.The computer unit of system 64 usually controls the treatment based on the most recently received actual GLNa, GLUCOSE and KETONE values. Therefore, at stage 908, the computer unit of system 64 begins processing. At stage 909, the computer unit of system 64 is adapted to receive an actual blood glutamine concentration value, GLNa, from a patient. In stage 910, the computer unit of system 64 is adapted to receive an actual blood glucose concentration value, GLUCOSEa, from a patient. In stage 911, the computer unit of system 64 is adapted to receive an actual blood concentration value of ketone bodies, KETONEa, from a patient. In stage 912, the system computer unit 64 controls the blood pump 60 and the dialysate pump 62, 68 in such a way that GLNaes is driven to or below GLNb. In simultaneous stage 914, the system computer unit 64 controls the blood pump 60 and the dialysate pump 62, 68 in such a way that GLUCOSEa is driven towards or below GLUCOSEAb. In simultaneous stage 916, the system computer unit 64 monitors GLNa, and if GLNa is less than GLNb, the system computer unit initiates and maintains the infusion of a composition containing glutamine or compounds containing glutamine in the extracorporeal blood circuit 52a, 52b. In simultaneous stage 918, the system computer unit 64 monitors GLUCOSEa, and if GLUCOSEa is less than GLUCOSEAb, the system computer unit initiates and maintains the infusion of a glucose-containing composition in the extracorporeal blood circuit 52a, 52b. At simultaneous stage 920, the system computer unit 64 monitors Ka, and if Ka is less than Kb, the system computer unit initiates and maintains the infusion of a composition containing ketone bodies into the extracorporeal blood circuit 52a, 52bo directly into the vascular system of the subject being treated. In some forms, the concentration of other substances in the blood can be controlled. For example, it has been found to be beneficial to lower the concentration of amino acids such as serine, glycine, and arginine from normal levels. In the perspective and partial front views of FIGURE 3 and FIGURE 4, an exemplary extracorporeal blood therapy system 110 that can implement the treatments and graphical user interfaces as described herein generally includes a blood tubing circuit 112 having first and second tubing segments 114 and 116 that are connected to a patient's vascular system 118 via access and return devices 117 and 119, respectively. Devices 117 and 119 may be cannulas, catheters, winged needles, or the like, as understood by someone skilled in the art. Tubing segments 114 and 116 are also connected to a filtration or processing unit 120. In dialysis, the filtration unit 120 is a dialyzer, which is also commonly referred to as a filter. Also included are numerous other components of the blood circuit 112, such as pressure sensors 127, 128, 154, and 129. Additional sensors may be provided to monitor glucose and / or glutamine concentrations; ketones (such as hydroxybutyrate (BHB), acetoacetate, and acetone); and / or cytokines (such as tumor necrosis factors (TNF) (e.g., TNF-α) and interleukins (e.g., IL-6)). However, as previously stated, the sensors may be placed in direct contact with the patient rather than within the blood circuit 112. When present, the sensors are operationally connected to the computer unit 12 via either a wireless or a physical connection. As shown schematically in FIGURE 5, the blood circuit 112, comprising the blood access line 114 and the blood return line 116, may also include a thermal management system 500 for heating or cooling the blood within the blood circuit 112. The thermal management system 500 is operatively connected to the computer unit 12, 64. This thermal management system can be used to heat the blood returning to the patient, for example, to approximately 37 °C. It can also be used to cool the returning blood to 20 °C or to raise the temperature of the returning blood to 43 °C, thereby warming the patient to a temperature of up to 38 to 40 °C. In addition, the dialysate circuit may also include a second thermal management system 501 to ensure that the blood has reached the desired temperature after passing through the blood filter 120. Also shown in FIGURE 3 and FIGURE 4 is the dialyzed or filtered fluid side of system 110, which generally includes a dialyzed fluid circuit 140 having the first and second dialyzed fluid pipe segments 141 and 142. Each of these pipe segments is connected to the filtration unit 120 on the opposite side of the membrane to the blood circuit segments 114, 116 112. In FIGURE 3 and FIGURE 4, a respective fluid pump 144, 146 is operatively associated with each of these pipe segments 141 and 142. The first pipe segment 141 is also connected to a dialysate fluid source (e.g., fluid bag 149), which may contain electrolytes or other premixed treatment compounds. The second pipe segment 142 is connected to a waste collection device (e.g., a waste container such as a bag). 153). A pressure sensor 154 may also be arranged in the second segment of dialysis fluid tubing 142. Figures 3 and 4 illustrate a system that is common as a basic model for numerous dialysis procedures. Additional fluid lines, circuits, and components can be added (or removed) to increase therapy options. In particular, in the present invention, an additional line can be provided for the delivery to the patient (for example, by adding ketones to the blood circuit 112) (for example, sodium hydroxybutyrate (BOHB), acetoacetate, and / or acetone). The delivery of ketones to the patient is important because it reduces the requirement for the patient to be in a state of diet-induced ketosis prior to the start of treatment. In modalities where a separate ketone supply is not provided, the fluid source bag 149 can also contain one or more ketones (such as sodium BOHB) in solution for diffusion across the membrane into the blood circuit. One or more of the dialysate fluid sources 149, the waste container 153, and the replacement fluid container 168 may be provided at the 400 scales that are in operational communication with the computing apparatus 12. Any additional ketone source may also be provided at such 400 scales. This allows the mass of fluid in each container to be monitored in use to provide an accurate record of the quantity of each fluid used or collected. Furthermore, as shown in FIGURE 3 and FIGURE 4, the system 110 includes an extracorporeal blood monitoring apparatus 160 that provides numerous treatment options, which can be controlled and / or monitored via the control / display screen 161 (e.g., a control apparatus or controller provided in a housing of the system 193). Touchscreen controls and / or other conventional knobs or buttons (not shown) may be incorporated (e.g., graphical user interfaces may be displayed via a touchscreen as described herein). Further detailed information on an example of apparatus 160 can be found in U.S. Patent Nos. 5,679,245, 5,762,805, 5,776,345, and 5,910,252, among others. A general dialysis treatment procedure, as performed, for example, with an apparatus described with reference to FIGURE 3 and FIGURE 4, will be described in general terms by way of example. First, blood is drawn from patient 118 through the access device 117 by, for example, the blood pump 124, and flows through the access line 114 to the filter 120. The filter 120 processes this blood according to one or more of a number of selected extracorporeal blood treatment profiles (for example, selected and controlled via the display interface 161 of the control apparatus 160). The treatment profiles also involve reducing glutamine and glucose levels in the patient's blood. Glutamine concentration is reduced to a value within the range of 0.1 to 0.5 mM, and preferably to a value within the range of 0.15 to 0.3 mM. Blood glucose concentration is reduced to a value within the range of 1 to 6 mM, and preferably to a value within the range of 2 to 4 mM. This treatment has a much more pronounced and adverse effect on cancer cells than on healthy cells in the body because the glycolysis and glutaminolysis pathways are enhanced in many cancer cells.While glycolysis is boosted to meet the increasing energy demands of cancer cells, glutaminolysis is also boosted in many cancer cells and can provide biosynthetic precursors, as well as playing an important role in maintaining reactive oxygen species (ROS) hemostasis. Inducing apoptosis in cancer cells by increasing ROS production is a key target for both radiation and chemotherapy. Finally, glutamine can act as a source of ATP during periods of low glucose levels. In some treatment modalities, the treatment profiles ensure that the patient's nutritional needs can be met by delivering an appropriate parenteral nutrition composition into the bloodstream or as a separate infusion directly into the patient's vascular system.In some modalities, blood ketone body concentrations are maintained within the range of 1 to 15 mM, and preferably within the range of 2 to 12 mM, throughout treatment. Although a patient is expected to produce their own ketone bodies (e.g., from consumed or infused lipids or body fat stores) when exposed to such low blood glucose concentrations, the biological process of producing sufficient ketone bodies may be slow to initiate. The introduction of ketone bodies during the treatments described herein ensures that the patient has a timely source of sufficient energy to sustain vital functions even when blood glutamine and glucose concentrations decline at an abnormally rapid rate. In certain treatments (especially those in which a high concentration of ketone bodies is maintained in the blood), the patient is provided with a supply of one or more pharmacological agents to help lower the blood glucose concentration. Such glucose-lowering agents preferably include biguanides, alpha-glucosidase inhibitors, SGLT2 inhibitors, and dopamine agonists. These agents may be delivered by the system by inclusion in the dialysate fluid source 149, the additional ketone source (if present), or as an additional infusion delivered to the blood circuit 112 or otherwise to the patient. Metformin is an example of a biguanide. Examples of alpha-glucosidase inhibitors include acarbose and miglitol. Examples of SGLT2 inhibitors include canagliflozin, dapagliflozin, and empagliflozin. Bromocriptine is an example of a dopamine agonist. In some preferred treatments, antiglycolytic agents may be administered to the patient to further inhibit glycolytic activity in tumor cells. Such agents may be delivered by the system through inclusion in the dialysate fluid source 149, the additional ketone source (if present), or as an additional infusion delivered to the blood circuit 112 or otherwise to the patient. Following treatment, the system returns the processed or treated blood to patient 118 through the return line 116 and the return device 119 inserted into the vascular system of patient 118 or otherwise connected to it. The blood flow path to and from patient 118, which includes the access device 117, the access line 114, the blood pump 124, the filter 120, as well as the return line 116 and the return device 119 back to the patient, forms the blood flow circuit 112. Pressure sensors can be used to detect various pressures in the system 110. For example, pressure sensor 127 can be connected in the access line 114 and allow monitoring of the fluid pressure in the access line 114, and a second pressure sensor 128 can be connected in the blood circuit 112 between the first blood pump 124 and the blood inlet at the filter 120 and can be used to detect and monitor the pressure of the blood supplied to the inlet of the filter 120. System 110 may further include a deaeration chamber 125 in the return line to provide a vortex path for expelling air from the blood. A filter replacement solution may be added to the deaeration chamber above the blood to prevent an air / blood interface. A degassing chamber monitoring line 191 may connect the degassing chamber 125 to an internal pressure transducer within the system housing 193 using a connecting device, such as a return pressure port 129. This allows for monitoring of the return pressure and, if necessary, the removal of air from the degassing chamber.A return clamp 131 connected in the blood circuit 112 selectively allows or terminates the flow of blood through the blood circuit 112 (e.g., the return clamp 131 can be activated whenever air is detected in the blood by the bubble detector 126). In addition, a pump 162 can be connected to an anticoagulant container 164 to deliver anticoagulant through an anticoagulant line 165 to the blood in the pipe segment 114, and a pump 166 can deliver replacement fluid from a replacement fluid container or bag 168 through a replacement fluid line 170. The secondary flow circuit 140 is also shown in Figure 3 and Figure 4 as it interacts with the filter 120. The secondary flow circuit 140 is connected to the secondary chamber of the filter 120. Extracorporeal material removed from the blood is removed from the secondary chamber of the filter 120 through the outlet pipe segment 142 of the secondary flow circuit 140, and extracorporeal material added to the blood moves to the filter 120 through the inlet pipe segment 141 of the secondary flow circuit 140. The secondary flow circuit 140 generally includes the fluid source, such as the bag 149, the inlet fluid line 141, the third pump 144, the secondary filter chamber 120, a waste fluid line 142, the pressure sensor 154, the fourth pump 146, and the waste collection device, such as the container 153. The source fluid bag 149 may contain a sterile dialysate, usually isotonic to blood, into which blood impurities will diffuse through the semipermeable membrane of the filtration unit 120. The source fluid bag may also include one or more ketones in solution for diffusion through the membrane into the blood circuit. Pump 144 is connected to the inlet fluid line 141 to supply dialysate from the dialysate source 149 to an inlet of filter 120. Waste collection container 153 is provided to collect or receive blood matter transferred through the semipermeable membrane in filter 120 and / or to receive used dialysate after it has passed through filter 120. A fourth pump, 146, is connected to the waste collection line 142 to move used dialysate from filter 120 to waste collection container 153. Pressure sensor 154 may also be located in the waste collection line 142 to monitor the pressure in the secondary chamber of filter 120. The filtration unit 120, the flow lines, and the other components of the primary and secondary flow circuits 112 and 140 described herein (with the exception, for example, of the pumps and perhaps some other elements) may be formed as an integral, replaceable unit (for example, an extracorporeal blood set). This integral, replaceable unit may be referred to herein as a “therapeutic assembly.” An example of such a therapeutic assembly, or integral, replaceable unit, is described in greater detail in U.S. Patent No. 5,441,636 entitled “Integrated Fluid Module for Blood Treatment” (see also U.S. Patent No. 5,679,245, entitled “Retaining Device for Extracorporeal Treatment Apparatus”). Depending on the system configuration, there may be therapy assemblies for performing different therapies. As can be seen in general in FIGURE 3 and FIGURE 4, the integrated tube and filter module (identified by part number 172) includes the filter 120 and all the related tubes and components described above that are connectable to the device 160. For example, the filter and tubing may be retained in a plastic support member 174, which is, in turn, connectable to the device 160 (e.g., connected to the system housing 193 of the device 160). Therapeutic assemblies may also include sensors that monitor the concentration of glucose and / or glutamine; ketones (such as bihydroxybutyrate (BHB), acetoacetate, and acetone); and / or cytokines (such as tumor necrosis factors (TNF) (e.g., TNF-α), interleukins (e.g., IL-6)).These sensors can be configured to monitor the concentration of the listed components in the bloodstream or they can be configured to monitor the concentration of the listed components through a direct interface with the patient's body. When in the operating position connected to the apparatus 160, the flexible fluid-conducting tubing lines to and from the filtration unit 120 are maintained in operational pump communication loops for operational contact with the peristaltic pumping members of pumps 124, 144, 146 and 166 to make the fluid flow through the primary (blood) and secondary (dialyzed fluid) circuits 112 and 140. The module 172, including the filter 120 and all associated tubing lines and flow components, can be disposed of after use. The peristaltic dome members of domes 124, 144, 146, and 166 can be permanently arranged in the apparatus 160 (without the disposable tubing components) and can be reusable. In general, electrical, mechanical, or electromechanical components are also permanently arranged in or on the apparatus 160 (e.g., connectable to the system housing 193 of the apparatus 160). Examples of such components include the display screen 161 (e.g., a touchscreen), the bubble detector 126, the line clamps 131, and the connecting devices for coupling to the pressure sensor devices used to implement the pressure sensors 127, 128, 129, 154, etc. Couplings for any required or preferred sensor can also be provided. As noted above, the access devices 117 and return devices 119 may include catheters. In some configurations, the catheters may include occlusion catheters, such as balloon occlusion catheters. This arrangement allows the access devices 117 and return devices 119 to be delivered to the tumor site (e.g., via the femoral artery or vein) as shown in Figure 4. This enables localized reduction of blood glucose concentration around the tumor and thus offers the possibility of further reducing blood glucose and / or glutamine levels. Reference example 1 A study was conducted on the sensitivity of different human cancer cell lines to the presence of glucose, glutamine, and ketones in the cell culture medium with the concomitant depletion of selected nutrients, to mimic the conditions obtained with cancer dialysis. Study 1 was conducted on a selection of human cancer cell lines established from renal cell carcinoma, colon carcinoma, and glioblastoma. The first study investigated the effect on cell viability of growth in the presence of increasing concentrations of ketonap-hydroxybutyrate, with concomitant restriction of glucose and glutamine levels. The addition of citrate to the cell culture medium was also tested. Cells were cultured under these conditions for three days, after which cell viability was determined. In the first study, the greatest effect on cell viability was observed when glutamine was removed from the culture medium. Materials and methods Cell culture conditions Established human colon carcinoma (HCT15, NCI-H508, and CQLQ205), renal cell carcinoma (769-P, 786-0, and RCC4), and glioblastoma (LN-18, A-172, and U-118MG) cell lines were selected for analysis. All cell lines were obtained from the American Type Culture Collection (ATCC, LGC standards, UK), except for RCC4 and HCT15, which were purchased from Sigma-Aldrich (Merck, Germany). Human renal cell carcinoma (RCC) primary cells isolated from patient nephrectomies were also included in the study. The culture conditions recommended by the American Type Culture Collection (ATCC) were followed, i.e., culturing the cells in DMEM medium with the addition of 1 mM sodium pyruvate, which was also added to RPMI-1640 medium to maintain the most similar conditions. Cells 769-P, RCC4, LN-18, A-172, U-118MG, and primary RCC cells were cultured in DMEM medium with high glucose content, while 786-0 HCT15, NCIH508, and COLO205 cells were cultured in RPMI-1640 medium according to ATCC recommendations. Both media were supplemented with 1% penicillin-streptomycin and 10% bovine serum. Cells were expanded, and aliquots were frozen according to standard procedures. The optimal seeding density for each cell line was determined in 96-well plates according to the “Protocol to optimize cell seeding densities to ensure growth in the logarithmic phase”. This protocol is as follows: • Prepare a single-cell suspension and measure the cell count / viability. Dilute the cells to approximately 160,000 cells / mL in complete medium. Add 200 pL of cells to the top row of a 96-well plate. Aliquot 100 pL of complete medium into all other wells. A small number of control wells of medium only are required in each plate to act as a blank. Repeatedly dilute the cell preparation 1 part in 2 down the plate using a 12-well channel pipette, i.e., 100 µL of cells added to 100 µL of medium in the row below. Then add 50 µL of complete medium to all wells. Cover the plate. • Incubate the plate overnight at 37 °C, 5% CO2. • Add 50 µL of fresh medium to the plate wells to achieve a final volume of 200 µL and incubate for 72 h at 37 °C, 5% CO2. • Measure viability using the CelITiter-Glo assay according to the manufacturer's protocol. • Plot the logarithmic number of cells against the intensity of luminescence to identify the cell concentration at which logarithmic growth is achieved. The CelITiter-Glo Luminescent (Promega) cell viability assay was used as a viability readout. Study 1. For each cell line, the previously determined optimum number of cells was seeded into 96-well plates on day 0. The following day, the cells were washed in PBS, and the medium was changed to either DMEM (Fisher Scientific) or RPMI-1640 medium (Saveen Werner) without glucose or L-glutamine, with the addition of nutrients as indicated in Table 3 and the "Plate Summary" file. Three wells were treated for each condition. After a 3-day incubation in the test condition medium, with daily medium changes, cell viability was determined using the CelITiter-Glo viability test. The experiment was repeated three times for each cell line. Table 1. Cancer cell lines and culture medium ινΐΛ / a / zuzz / u 1 o 1 / 1 kidney 769-P DMEM with high glucose content 786-0 RPMI-1640 RCC4 High-Glucose DMEM Colon HCT15 RPMI-1640 NCI-H508 RPMI-1640 COLO205 RPMI-1640 Brain CRL2610 (LN-18) High-Glucose DMEM A-172 High-Glucose DMEM U-118MG High-Glucose DMEM Table 2. Content of normal culture medium in selected nutrients. Medium Glucose (g / L) L-glutamine (mM) NaHCO3 (g / L) HEPES (mM) NaPyr (mM) RPMI-1640 2 (11mM) 2 2 25 0(1) DMEM with high glucose content 4.5 (25mM) 4 3.7 (1.5) 0 1 Table 3. Test conditions Study 1. BOHB (mM) Glucose* 0 4 12 w glutamine 100% + / -citrate 25% + / -citrate 0% + / -citrate w / o glutamine 100% + / -citrate 25% + / -citrate 0% + / -citrate Matrix showing the combination of different growth conditions used in Study 1. *The amount of glucose is presented as the percentage of the concentration present in the standard culture medium for each cell line. Where indicated, 1 mM citrate was added to the culture medium. The indicated nutrients were added to DMEM (Fisher Scientific) or RPMI-1640 (Saveen Werner) medium without glucose or L-glutamine. Table 4: Information on product ordering product company Product number CELLULAR LINES 786-0 [786-0] (ATCC® CRL-1932™) ATCC CRL-1932 COLO 205 (ATCC® CCL-222™) ATCC CCL-222 A-172 [A172] (ATCC® CRL-1620™) ATCC CRL-1620 769-P (ATCC® CRL-1933™) ATCC CRL-1933 NCI-H508 [H508] (ATCC®CCL-253™) ATCC CCL-253 LN-18 (ATCC®CRL-2610™) ATCC CRL-2610 U-118 MG (ATCC®HTB-15™) ATCC HTB-15 RCC4 plus vector only Carcinoma of Renal cells sigma 03112702- 1VL HCT-15 HUMAN COLON ADENOCARCINOMA sigma 91030712- 1VL CELL CULTURE MEDIUM DMEM / high glucose with 4.0mM L-glut, with sodium pyruvate Nordic Biolabs SH30243.01 RPMI 1640 with 25 mM HEPES with L-Glut Nordic Biolabs SH30255.01 500ML DMEM WO GLUC & PHENOL RED Fisher Se 12307263 RPMI 1640 Medium, without D-Glucose, without L-Glutamine, 500mL saveen werner 01 -101-1A CELL CULTURE PLASTICS 96-well plates, white, transparent bottom, with lid Fisher Se (Corning) 10517742 Opaque white tape, BackSeal support tape perkin elmer 6005199 cell strainer 40pm Saween Werner 93040 cell strainer 40pm filcons BD 340621 VIABILITY TEST CelITiter-Glo Promega G7571 CHEMICALS AND ADDITIVES DMSO sigma D2650-5x5mL Glucose L-glutamine Fisher Se 11500626 PEST Nordic Biolabs SV30010 trypsin Nordic Biolabs SH30042.01 sodium citrate sigma PHR1416-1g sodium crystal of DL-B-hydroxybutylic acid sigma H6501-5g The results of Study 1 are presented in the graphs in FIGURE 6A, FIGURE 6B, FIGURE 6D, FIGURE 6E, FIGURE 6F, FIGURE 6G, FIGURE 6H, FIGURE 6I, and FIGURE 6J. A clear relationship is shown between a reduction in glutamine present in the cell culture medium and a reduction in cell proliferation. Study 2 As noted previously, Study 1 followed the ATCC-recommended culture conditions. However, pyruvate is a potential energy source that could affect the results. Therefore, in Study 2, the same culture conditions as in Study 1 were tested in two of the cell lines, A172 (glioblastoma) and RCC4 (renal cell carcinoma), in DMEM medium without the addition of sodium pyruvate. The results are presented in Figure 7A, Figure 7B, Figure 7C, and Figure 7D. As in Study 1, a clear relationship was shown between the reduction of glutamine present in the cell culture medium and the reduction of cell proliferation. However, in the absence of pyruvate in the cell culture medium, the results were much more pronounced. Similarly, an increase in the concentration of the ketone BOHB also appears to suppress cell proliferation. All patents, patent documents, and references cited herein are incorporated herein in their entirety as if each were incorporated separately. This disclosure is provided with reference to illustrative embodiments and is not intended to be construed in a limiting manner. As described above, a person skilled in the art will recognize that various other illustrative applications may utilize the techniques described herein to take advantage of the beneficial features of the apparatus and methods described herein. Various modifications of the illustrative embodiments, as well as additional embodiments of the disclosure, will be apparent upon reference to this description. Example 2 Studio design Growth medium To study the effect of a nutrient-restricted ketogenic environment on cancer cell growth in vitro, three different cell culture media were formulated. Medium A was the complete RPMI1640 medium in which cell lines are routinely cultured. Medium B was used to approximate the conditions found in normal human serum. Glucose, glutamine, serine, glycine, and arginine levels were adjusted to match normal physiological levels found in human serum. These nutrients were selected based on their use as energy sources and their effects on the metabolic state of cancer cells. Medium C was used to emulate the nutrient-restricted ketogenic condition of cancer dialysis. Here, the levels of the selected nutrients were reduced to half the physiological levels in Medium B, and the ketone body BOHB was added. The composition of each medium is described in the materials and methods and is listed in Table 5-6. Oxygen levels Human cancer cell lines are routinely established and cultured at atmospheric oxygen levels (21% O2); however, physiological oxygen levels in tissues are considerably lower, ranging from 3% to 13%. Within the tumor microenvironment, the rapid growth rate of cancer cells, combined with an often malformed and defective vasculature, typically results in hypoxic regions with oxygen levels ranging from 0% to 5%. Given the effects of oxygen levels on energy metabolism, and to further mimic physiological conditions in vivo, the growth of cancer cell lines was studied in media A, B, and C under both ambient conditions (21% O2) and more physiological conditions (5% O2). Ketones The ketone bodies acetoacetate (Acac), BOHB, and acetone are produced by the liver during fasting or starvation. BOHB is the main ketone body in mammals, while Acac constitutes about 20%. Most published in vitro studies investigating the effect of ketones on cancer cells focus primarily on BOHB; however, some studies suggest different effects of adding Acac compared to BOHB. To further mimic the in vivo ketogenic state in which both ketones are present, and to investigate a possible differential effect of BOHB and Acac, Acac was also included in the study. Materials and methods Cell lines All cell lines were acquired from ATOO (ATOO, LGC standards) except for RCC4, which was from Sigma-Aldrich (Merck). Primary human renal cell carcinoma cells were isolated from nephrectomies performed at Sahlgrenska University Hospital in Gothenburg, Sweden, after obtaining informed patient consent and approval from the regional ethics committee. The optimal seeding density for each cell line was determined in 96-well plates cultured for 3 days in standard cell culture medium. Growing conditions and additives Cells were maintained in RPMI-1640 medium (31870-025 GIBCO) with the addition of 10% serum, 200 mM L-glutamine, and 1% penicillin-streptomycin (PEST) in humidified chambers at 37°C and 5% CO2. For hypoxic conditions (5% O2), cells were maintained in a Galaxy 14 S CO2 incubator (Eppendorf) where N2 was used to adjust the O2 level to 5%. Media A, B, and C were prepared as follows. Medium A: RPMI1640 (31870-025, GIBCO) with the addition of 1% PEST, 200 mM L-glutamine, and 10% dialyzed whey. Dialyzed whey was used to reduce the amounts of small molecules, such as amino acids. Media B and C were prepared from modified RPMI1640 medium powder without L-glutamine, glucose, or amino acids (R9010-01, US Biological Life Sciences). For 1 L of medium, 7.4 g of powder were dissolved in 900 mL of sterile, unheated water, and 2 g of sodium bicarbonate were added. The amino acids listed in Table 5 were added at the same concentration as in the complete RPMI1640 medium (Table 5). After all additions, the medium was sterilized by filtration through 0.22 µm membranes and divided into two flasks. In medium B, to mimic physiological conditions, the levels of glutamine, serine, glycine, arginine, and glucose were adjusted to the median of the levels measured in human serum, based on data from the Mayo Clinic laboratories (https: / / www.mayocliniclabs.com / test-cataloq / Clinical+and+interpretive / 9265). To model cancer dialysis conditions in medium C, the levels of these nutrients were reduced to 50% of physiological levels. As in medium A, 1% PEST and 10% dialyzed serum were added to media B and C. The concentrations of the selected nutrients in medium AC are summarized in Table 6. Sodium pyruvate, a common addition to cell culture media, was not present in any of the media used. Table 5. Amino acid concentrations in RPMI1640 ινΐΛ / a / zuzz / uioi ri Amino acids (g / L) dissolved in L-Asparagine 0.0568 h2o L-aspartic acid 0.02 1M HCI L-Cystine 0.065 2M HCI L-glutamic acid 0.02 IMdeHCI L-Histidine 0.02 H2O Hydroxy-L-proline 0.02 h2o L-lsoleucine 0.05 1M HCI L-Leucine 0.05 1M HCI L-Lysine 0.04 h2o L-Methionine 0.015 h2o L-Phenylalanine 0.015 1M HCI L-Proline 0.02 H2O L-Threonine 0.02 h2o L-Tryptophan 0.005 1M HCI L-Tyrosine 0.024 1M HCI L-Valine 0.02 H2O Table 6. Nutrient composition of media A, B and C. Medium A RPMI-1640 Medium B Physiological Medium C Cancer Dialysis Glucose (mM) 11 5.85 2.93 BOHB (mM) 0 0 8 Glutamine (uM) 2000 664 332 Serine (uM) 280 125 62.5 Glycine (uM) 130 308 154 Medium C Medium A Medium B dialysis of RPMI-1640 physiological cancer Arginine (uM) 11150 176 138 iviA / a / zuzz / u ι oi / i The amino acids and other additives were sourced from Sigma Aldrich. After adding all the nutrients, the pH was measured. The pH values ​​were as follows: RPMI1640 complete with 10% non-dialyzed FBS, 1% PEST and 200mM L-glutamine, pH 7.78; Medium A, pH 7.56; Medium B, pH 7.62 and Medium C, pH 7.57. Stock solutions of sodium salt of DL-p-hydroxybutyric acid (H6501, Sigma Aldrich) and lithium acetoacetate (A8509, Sigma Aldrich) were prepared in water, filtered under sterile conditions, aliquoted, and stored at -20 °C. Lithium chloride (L7026, Sigma Aldrich) was used as a control for the addition of lithium to Li-Acac. Feasibility study The CelITiter-Glo Luminescent cell viability assay (Promega) was used to determine cell counts according to the manufacturer's instructions. In the experiments shown in Figure 12 and Figure 13, double plates were seeded and treated. One set of plates was used to collect the medium for lactate measurement (see below) and the CelITiterGIo assay. The other set of plates was frozen at -80 °C at the end of the experiment. The frozen plates were then used for the CyQuant cell proliferation assay (Thermo Fisher), which measures the amount of DNA per well. Analyzing cell counts using both the CelITiterGIo and CyQuant assays ensured that the effects of culture conditions on viability or growth rate were not masked by simultaneous changes in ATP levels per cell. Collection of the medium for lactate measurement In the experiments shown in Figure 12 and Figure 13, the cell culture medium was harvested on day 3, transferred to new 96-well plates, and frozen at -80 °C. This medium can be used to analyze the amount of lactate excreted as a measure of metabolic status. Several kits are available for lactate measurement; for example, the Lactate-Glo assay (J5021, Promega) is designed for use in assays involving serum. RESULTS Example 2 was designed to answer the following question: Is the growth of selected cancer cell lines affected by the cancer dialysis conditions emulated in medium C under normoxia or hypoxia? Growth in media A, B and C As a first step, media A to C were prepared as described in Materials and Methods, and the ability of cancer cell lines to grow in these media was tested. Growth curves were established for the selected cell lines over time in each medium. The number of cells was analyzed after 1, 2, and 3 days of culture in medium A to C under normoxia (21% O2). As shown in FIGURE 10, reducing the selected nutrients to more physiological levels, as in medium B, significantly reduced the growth rate of the A549 lung carcinoma and RCC4 renal carcinoma cell lines compared to medium A. Medium C further reduced growth rates compared to medium A. Growth of cancer cells in AC media under normoxia and hypoxia Figure 11 shows the cell counts after 3 days of culture in media A to C under normoxia and hypoxia for the A549 lung carcinoma and RCC4 renal cell carcinoma cell lines, as well as for primary renal carcinoma (ROO) cells. Again, the growth rate under normoxia was reduced in media B and C compared to medium A. The same pattern was observed in cells cultured at 5% O2. Again, in RCC4, the low nutrient levels and the addition of BOHB in medium C did not have a significant additional effect compared to the conditions in medium B. In the case of A549, a small but significant reduction in the growth rate was found between medium B and C, but only under normoxia. This study included primary renal cell carcinoma cells from three patients. Similar to established cell lines, these cells showed a reduced growth rate in media B and C compared to medium A. In general, the change in oxygen pressure from 21% (normoxia) to 5% O2 (hypoxia) had a very limited effect on the growth rate of these cells. Next, it was decided to also include Acac in the study and analyze the viability of cells cultured in the presence of BOHB and Acac alone or in combination in AC Medium. The experiment was performed at 21% and 5% O2. The experiments were performed with the A172 and U118MG glioma cell lines. As a chiral molecule, BOHB exists as two enantiomers, D- and L-BOHB. D-BOHB is normally produced and metabolized in humans. The BOHB salt used in this study contains a 50:50 mixture of D- and L-BOHB. To ensure a high presence of the active D-form, the total concentration of added BOHB was increased to 16 mM, resulting in a D-BOHB level of 8 mM. To maintain a constant total concentration of active ketones, 8 mM of Acac was used, and for the combination of both ketones, the levels were adjusted to 4 mM Acac and 8 mM BOHB (containing 4 mM D-BOHB). The Acac available for in vitro use is in the form of a lithium salt. Since lithium can affect the viability of cancer cells, 8 mM LiCl was used as a control for the 8 mM Acac data and 4 mM LiCl for the 4 mM Acac / 8 mM BOHB data. At the end of the experiment, the culture medium from each well was collected and frozen to allow for subsequent determination of lactate levels as a measure of metabolic status. In addition, duplicate experiments were performed, in which one set of plates was frozen for subsequent quantification of cell numbers using the CyQuant proliferation assay, and the cell counts in the other set were analyzed using the CelITiterGIo viability assay. The effect of BOHB and Acac added alone or in combination As shown in FIGURE 12 and FIGURE 13, the initial experiment yielded promising data on the effect of high ketone concentration under nutrient-reduced conditions on the growth of A172 and U118MG glioma cell lines. In medium A, under both normoxia and hypoxia, the addition of 16mM BOHB alone had no growth-inhibiting effect on A172 or U118MG cells, and 8mM Acac did not further reduce the number of cells compared to the 8mM LiCI control. However, the addition of 4Mm of Acac in combination with 8mM of BOHB significantly reduced the number of A172 cells in Medium A under normoxia compared to the 4mM LiCI control. The interpretation of the results for medium B was affected by a technical error in the normoxic control sample. However, in hypoxic A112 cells, BOHB significantly reduced the cell count to approximately 70% of the amount in medium B without BOHB. A similar reduction was also observed in hypoxic U118MG cells. Furthermore, in medium B, 8mM of Acac significantly reduced the number of cells compared to the 8mM LiCI control in both cell lines, but only at 21% O2. In medium C, the addition of 8 mM Acac alone did not significantly reduce the number of cells compared to the 8 mM LiCI control. However, in both cell lines and at both 21% and 5% O2, the addition of 16 mM BOHB significantly reduced the number of cells to approximately 30% compared to medium C without BOHB. The combination of BOHB and Acac also resulted in a significantly lower number of cells in medium C compared to the 4mM LiCI control, in both cell lines and at both oxygen levels. These results suggest that the addition of high levels of BOHB or Acac alone does not inhibit glioma cell growth in a nutrient-rich environment such as medium A. Even in medium B, with more physiological nutrient levels, only small differences were observed when ketones were added. The greatest effects were found in medium O, where both 16 mM BOHB alone and the combination of 8 mM BOHB with 4 mM Acac significantly reduced cell numbers compared to their respective controls, under both hypoxic and normoxic conditions. This was not observed when 8 mM Acac was added alone. However, repeating these experiments, focusing on media B and C under normoxic conditions, yielded inconsistent results. Figures 14, 15, and 16 show the combined results of experiment 2-6 for the A172 and U118MG glioma cell lines and the RCC4 renal cell carcinoma cell line. A trend toward reduced growth was observed in medium C when BOHB or Acac was added separately, particularly in the A172 cell line. The results from the first and second parts of Example 2 indicated that the cancer cell lines grew more slowly in a nutrient-restricted medium. The cell lines tested appeared viable in media B and C, although the proliferation rate was reduced. Optical inspection of the cells on day 3 revealed no floating cells, which could have been a sign of cell death. Data from the third part of the study show increased sensitivity of glioma cell lines to high levels of BOHB or to a combination of BOHB and Acac in nutrient-restricted medium C.

Claims

1. An extracorporeal blood therapy system (50) for treating a subject suffering from cancer, characterized in that the system comprises: an extracorporeal blood circuit (52a, 52b); a dialyzed fluid circuit (54a, 54b); said extracorporeal blood circuit (52a, 52b) and the dialyzed fluid circuit (54a, 54b) are separated by a membrane (59) from a filtration unit (58); at least one blood pump (60) for controlling the flow of blood through the blood circuit (52a, 52b); at least one dialyzed fluid pump (62, 68) for controlling the flow of dialyzed fluid through the dialyzed fluid circuit (54a, 54b); Optionally, one or more infusion lines (66, 80, 81, 82), each infusion line being connected to the extracorporeal blood circuit (52a, 52b) or adapted to be connected directly to the vascular system of the subject to be treated, each infusion line comprising an infusion pump;a system computing unit (64) operatively connected to the blood pump (60) and the dialysate fluid pump (62, 68) and, optionally, to one or more infusion pumps of one or more infusion lines (66, 80, 81, 82), said system computing unit having a user interface including an input means and a display means; wherein the system computing unit (64) is adapted to receive a desired blood concentration value GLNb of glutamine (901) within the range of 0.1 and 0.5 mM; the system computing unit (64) is adapted to receive a desired blood concentration value GLUCOSAb of glucose (903) within the range of 2 to 4 mM;The system computing unit (64) is adapted to receive a desired blood concentration value KETONAb of a ketone body such as acetoacetate, beta-hydroxybutyrate or pharmaceutically acceptable derivatives, esters and salts thereof (905) within the range of 1 to 15 mM; the system computing unit (64) is adapted to receive a GLNp concentration value representing the concentration of glutamine or pharmaceutically acceptable glutamine-containing compounds in the fresh dialysate fluid (902); the system computing unit (64) is adapted to receive a GLUCOSAp concentration value representing the glucose concentration in the fresh dialysate fluid (904);Optionally, the system computer unit (64) is adapted to receive a KETONEp concentration value, representing the concentration of a ketone body, such as acetoacetate, beta-hydroxybutyrate or pharmaceutically acceptable derivatives, esters and salts thereof in the fresh dialysate fluid (907); optionally, the system computer unit (64) is adapted to receive a KETONEi concentration value representing the concentration of a ketone body, such as acetoacetate, beta-hydroxybutyrate or pharmaceutically acceptable derivatives, esters and salts thereof in an infusion fluid to be infused into the extracorporeal bloodline (52b) or directly into the vascular system of said subject to treatment through one of said infusion lines (66, 80, 81, 82) (906);the system computer unit (64) is adapted to receive an actual GLNa blood concentration value of glutamine from said treated subject (909) and to receive an actual blood GLCOSAa blood concentration value of glucose from said treated subject (910) and to receive an actual KETONEa blood concentration value of a ketone body such as acetoacetate and / or beta-hydroxybutyrate (911); the system computer unit (64) is adapted to control said blood pump (60) and said dialysate fluid pump (62, 68) so that the actual GLNa blood concentration value of glutamine is driven to or below GLNb (912) and the actual GLCOSAa blood concentration value of glucose is driven to or below GLUCOSAb (914);and if the system (50) comprises one or more of said infusion lines (66, 80, 81,82) and in the event that one of said infusion lines (66, 80, 81,82) is adapted to infuse said infusion fluid into the extracorporeal blood line (52b) or directly into the vascular system of said subject to treatment, the computer unit of the system (64) is adapted to control said infusion pump of said infusion line so that the actual blood concentration value of KETONEa is driven towards KETONEAb (920); or alternatively if the system (50) does not comprise said infusion line (66,80, 81,82), the system's computer unit (64) is adapted to compare KETONEa and KETONEAb, and if KETONEa < KETONEAb, display a message on said screen informing that the treated subject should consume an additional amount of ketone bodies or medium-chain triglycerides.; 2. An extracorporeal blood treatment system (50) according to claim 1, characterized in that the system (50) comprises one or more of said infusion lines (66, 80, 81, 82), and the calculation unit of the system (64) is adapted to receive a KETONEa concentration value representing the concentration of a ketone body such as acetoacetate, beta-hydroxybutyrate, or pharmaceutically acceptable derivatives, esters, and salts thereof in an infusion fluid to be infused into the extracorporeal blood line (52b) or directly into the vascular system of the subject to be treated, through one or more of said infusion lines (66, 80, 81, 82) (906), and the computer unit of the system (64) is adapted to control said infusion pump of said infusion line in such a way that the actual blood concentration value of KETONEa is routed to KETONEAb (920).

3. An extracorporeal blood treatment system (50) according to claim 2, characterized in that the computer unit of the system (64) is adapted to monitor GLNa and initiate the infusion of a pharmaceutically acceptable glutamine-containing composition or glutamine-containing compounds if GLNa is less than GLNb (916), by starting a relevant infusion pump in one or more infusion lines (66, 80, 81, 82), and maintaining said infusion until GLNa is equal to GLNb.

4. An extracorporeal blood treatment system (50) according to any of claims 2 to 3, characterized in that the system's computer unit (64) is adapted to monitor GLUCOSAa, and initiate the infusion of a glucose-containing composition if GLUCOSAa is less than GLUCOSAb (918) by starting a relevant infusion pump in one or more infusion lines (66, 80, 81, 82), and maintaining said infusion until GLUCOSAa is equal to GLUCOSAb (918).

5. A system in accordance with any of the preceding claims, characterized in that the filtration membrane has a cutoff molecular weight (MWCO) of less than 60 kDa.

6. A system according to claim 5, characterized in that the filtration membrane has an MWCO of less than approximately 50 kDa or less than approximately 40 kDa (such as less than 30 kDa, less than 10 kDa, less than 5 kDa or less than 2 kDa).

7. A system in accordance with any of the preceding claims, characterized in that the blood circuit comprises a thermal management system for heating or cooling the blood in the blood line during use.

8. A system according to claim 7, characterized in that the thermal management system is controllable to regulate the temperature of the blood in the blood circuit to a temperature between 20 °C and 43 °C.

9. A system according to any of the preceding claims, characterized in that it further comprises one or more sensors (S, 90, 91, 92, 93) for the detection of analytes selected from the group of glucose, glutamine, and ketone bodies, the sensors (S, 90, 91, 92, 93) being preferably located in a portion thereof in the fresh dialyzed fluid (907); optionally, the computer unit of the system (64) is adapted to receive a KETONE infusion fluid concentration value of a ketone body (906); the computer unit of the system (64) is adapted to receive a real blood GLN a concentration value of glutamine (909); the computer unit of the system (64) is adapted for a real blood GLC a concentration value of glucose (910);the system computer unit (64) is adapted to receive a true blood concentration value KETONEa of a ketone body such as beta-hydroxybutyrate and / or acetoacetate (911); the system computer unit (64) is adapted to control said blood pump (60) and said dialysate fluid pump (62, 68) so that the true blood concentration value GLNa of glutamine is driven to or below GLNb (912) and the true blood concentration value GLUCOSEa of glucose is driven to or below GLUCOSAb (914); and in the event that an infusion pump is operatively connected to the system computer unit (64), the system computer unit (64) is adapted to control the infusion pump so that the true blood concentration value KETONEa is driven to KETONEAb (920);and in the event that no infusion pump is operationally connected to the system computer unit (64), the system computer unit (64) is adapted to compare KETONEa and KETONEAb, and if KETONEa < KETONEAb, to display a message on said screen informing that the treated subject should consume an additional amount of ketone bodies or medium-chain triglycerides.; 12. A dialysis fluid, characterized in that it comprises ketone bodies such as acetoacetate, beta-hydroxybutyrate or pharmaceutically acceptable derivatives, esters and salts thereof, for use in cancer dialysis therapy.

13. A dialysis fluid for use in cancer dialysis therapy treatment according to claim 12, characterized in that it further comprises at least one of a) glutamine or glutamine-containing compounds; and b) glucose.

14. A dialysis fluid for use in cancer dialysis therapy treatment according to claim 12, characterized in that the concentration of: a) glutamine or glutamine-containing compounds ranges from 0 to 0.5 mM, and preferably from 0.05 to 0.3 mM; b) glucose ranges from 0 to 6 mM and, preferably, from 0.5 to 4 mM; and c) ketone bodies range from 1 to 15 mM and preferably from 2 to 12 mM.

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