Effect of ultrafiltration on extravascular lung water assessed by lung ultrasound in children undergoing cardiac surgery: a randomized prospective study.

BACKGROUND: Increased lung water and the resultant atelectasis are significant pulmonary complications after cardiopulmonary bypass (CPB) in children undergoing cardiac surgery; these complications are observed after CPB than after anaesthesia alone. Ultrafiltration has been shown to decrease total body water and postoperative blood loss and improve the alveolar to arterial oxygen gradient and pulmonary compliance. This study investigated whether conventional ultrafiltration during CPB in paediatric heart surgeries influences post-bypass extravascular lung water (EVLW) assessed by lung ultrasound (LUS). METHODS: This randomized controlled study included 60 patients with congenital heart disease (ASA II-III), aged 1 to 48 months, with a body weight > 3 kg. Conventional ultrafiltration targeting a haematocrit (HCT) level of 28% was performed on the ultrafiltration group, while the control group did not receive ultrafiltration. LUS scores were recorded at baseline and at the end of surgery. The PaO2/FiO2 ratio (arterial oxygen tension divided by the fraction of inspired oxygen), urine output, and haemodynamic parameters were also recorded. RESULTS: LUS scores were comparable between the two groups both at baseline (p = 0.92) and at the end of surgery (p = 0.95); however, within the same group, the scores at the end of surgery significantly differed from their baseline values in both the ultrafiltration (p = 0.01) and non-ultrafiltration groups (p = 0.02). The baseline PaO2/FiO2 ratio was comparable between both groups. at the end of surgery, The PaO2/FiO2 ratio increased in the ultrafiltration group compared to that in the non-ultrafiltration group, albeit insignificant (p = 0.16). no correlation between the PaO2/FiO2 ratio and LUS score was found at baseline (r = - 0.21, p = 0.31). On the other hand, post-surgical measurements were negatively correlated (r = - 0.41, p = 0.045). CONCLUSION: Conventional ultrafiltration did not alter the EVLW when assessed by LUS and oxygenation state. Similarly, ultrafiltration did not affect the urea and creatinine levels, intensive care unit (ICU) stays, ventilation days, or mortality. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT03146143 registered on 29-April-2017.

Pharmaceutical applications of affinity-ultrafiltration mass spectrometry: Recent advances and future prospects.

The immunoaffinity of protein with ligand is broadly involved in many bioanalytical methods. Affinity-ultrafiltration mass spectrometry (AUF-MS), a platform based on interaction of protein-ligand affinity, has been developed to fish out interesting molecules from complex matrixes. Here we reviewed the basics of AUF-MS and its recent applications to pharmaceutical field, i.e. target-oriented discovery of lead compounds from combinatorial libraries and natural product extracts, and determination of free drug concentration in biosamples. Selected practical examples were highlighted to illustrate the advances of AUF-MS in pharmaceutical fields. The future prospects were also presented.

Association of haemodynamic changes measured by serial central venous saturation during ultrafiltration for acutely decompensated heart failure with diuretic resistance and change in renal function.

BACKGROUND: Patients with acute decompensated heart failure with diuretic resistance (ADHF-DR) have a poor prognosis. The aim of this study was to assess in patients with ADHF-DR, whether haemodynamic changes during ultrafiltration (UF) are associated with changes in renal function (Δcreatinine) and whether Δcreatinine post UF is associated with mortality. METHODS: Seventeen patients with ADHF-DR underwent 20 treatments with UF. Serial bloods (4-6 hourly) from the onset of UF treatment were measured for renal function, electrolytes and central venous saturation (CVO2). Univariate and multivariate analysis were performed to assess the relationship between changes in markers of haemodynamics [heart rate (HR), systolic blood pressure (SBP), packed cell volume (PCV) and CVO2] and Δcreatinine. Patients were followed up and mortality recorded. Cox-regression survival analysis was performed to determine covariates associated with mortality. RESULTS: Renal function worsened after UF in 17 of the 20 UF treatments (baseline vs. post UF creatinine: 164±58 vs. 185±69µmol/l, P<0.01). ΔCVO2 was significantly associated with Δcreatinine [ß-coefficient of -1.3 95%CI (-1.8 to -0.7), P<0.001] and remained significantly associated with Δcreatinine after considering changes in SBP, HR and PCV [P<0.001]. Ten (59%) patients died at 1-year and 15(88%) by 2-years. Δcreatinine was independently associated with mortality (adjusted-hazard ratio 1.03 (1.01 to 1.07) per 1µmol/l increase in creatinine; P=0.02). CONCLUSIONS: Haemodynamic changes during UF as measured by the surrogate of cardiac output was associated with Δcreatinine. Worsening renal function at end of UF treatment occurred in the majority of patients and was associated with mortality.

Beneficios del descanso peritoneal / Benefits of peritoneal rest

Introducción: Valorar si el descanso peritoneal, de al menos un día semanal, ha supuesto mejoras en la rehabilitación de los pacientes y el impacto clínico que puede suponer. Nos planteamos además cuantificar el beneficio económico. Material y Método: Se realizó un estudio longitudinal, retrospectivo, descriptivo. De los pacientes atendidos en nuestra unidad desde el 1 de enero de 2014 al 31 de diciembre de 2014, se estudiaron los pacientes que cumplieran todo el año de seguimiento y que no procedieran de otras técnicas de depuración como la hemodiálisis o trasplante renal. La muestra de estudio estuvo compuesta por 40 pacientes, de los que 21 tuvieron prescrito al menos 1 día semanal de descanso peritoneal y 19 pacientes sin descanso. Se recogieron las siguientes variables al inicio del periodo de estudio y a los 12 meses: Variables demográficas, variables relacionadas con el estado de volumen, datos clínicos relacionados con la técnica, se pasó una encuesta de satisfacción a todos los pacientes estudiados, y se recogieron los importes del coste mensual de cada tipo de tratamiento. Resultados: Las diferencias iniciales entre los grupos, eran esperables ya que son los valores en los cuales se ha basado la prescripción del día de descanso. La exposición a la glucosa, al comienzo y al final fue menor en el grupo con descanso. Al año, no se encontró diferencias en los parámetros estudiados. Una encuesta de satisfacción nos reveló a que dedican los pacientes el día de descanso y los que no lo tienen a que lo dedicarían. Conclusiones: El descanso peritoneal no ha supuesto una peor evolución de los parámetros clínicos estudiados al año de seguimiento, cumpliendo las recomendaciones de adecuación de diálisis de las guías clínicas. La exposición a la glucosa, aun sin llegar a ser significativa por la duración del estudio, ha sido menor en el grupo con descanso. El día de descanso ha facilitado a los pacientes mejorar su rehabilitación social principalmente. Los días de descanso han supuesto un ahorro de al menos 13,33% en la factura mensual (AU)

Introduction: To assess whether the peritoneal rest at least one day a week has led to improvements in the rehabilitation of patients, and the clinical impact that can be achieved. We also propose to quantify the economic benefit. Material and methods: A longitudinal, retrospective, descriptive study was conducted. Of those patients seen in our unit from 1 January 2014 to 31 December 2014, patients who fulfilled all the monitoring year and that at the same time they were not subjected to other purification techniques such as dialysis or transplantation kidney were studied. The study sample was composed of 40 patients, of whom 21 had prescribed at least 1 weekly day of peritoneal rest, and 19 patients without rest. The following variables at baseline and 12 months of the study period were recorded: Demographic variables, variables related to volume status, clinical data related to the technique and data related to a satisfaction survey, as well as the amounts of the monthly cost of each type of treatment. Resultados: The initial differences between the groups were expected since they are the values on which is based the prescription of the rest day. Exposure to glucose at the beginning and the end was lower in the group with rest. At one year, no differences in the studied parameters were found. A satisfaction survey revealed to us the activity that patients spend the rest day, as well as the activity that would perform those who not rest. Conclusiones: The peritoneal rest has not meant a worse outcome of the clinical parameters studied at one year, fulfilling the recommendations of dialysis adequacy of the guidelines. Although not statistically significant for the duration of the study, exposure to glucose was lower in the group with rest. The rest day has mainly provided to patients to improve their social rehabilitation. Rest days have generated savings on the monthly bill of 13.33% (AU)

Análisis de la sobrecarga del cuidador del paciente en diálisis peritoneal / Analysis of caregiver burden in peritoneal dialysis patients

Introducción: Un hecho diferencial de la diálisis peritoneal ambulatoria es la necesidad de colaboración de un cuidador principal que se responsabiliza del tratamiento del paciente. Esto unido al carácter crónico de esta patología y posible dependencia del paciente provoca cambios en el estilo de vida del cuidador principal siendo por tanto, una persona expuesta a la sobrecarga. Objetivo: Identificar el grado de sobrecarga de los cuidadores de pacientes en diálisis peritoneal ambulatoria en el Hospital Reina Sofía de Córdoba y su relación con la calidad de vida y la dependencia del paciente. Pacientes y métodos: Se realizó un estudio observacional descriptivo y transversal. Se estudiaron 18 pacientes en tratamiento con diálisis peritoneal ambulatoria y sus respectivos cuidadores. Se incluyó a todos los cuidadores y pacientes que aceptaron colaborar, previo consentimiento informado. Se utilizó el cuestionario SF-36 para evaluar la calidad de vida del paciente junto con el test de Zarit y un cuestionario de sobrecarga de los cuidadores de pacientes en diálisis peritoneal ambulatoria. Con éste último, también se identificó el nivel de dependencia del enfermo desde el criterio del cuidador. Resultados: Respecto a la calidad de vida, se encuentra una disminución leve de algunas de las dimensiones de la población general para la misma edad. No se encontró sobrecarga en la mayoría de los cuidadores principales con ninguno de los instrumentos usados. Se encontró una correlación directa entre ambos instrumentos. En cuanto al nivel de dependencia, un 83 % de pacientes eran independientes y un 17 % de pacientes eran dependientes. Conclusión: A la vista de estos resultados, podemos concluir que, al menos en la muestra estudiada se encuentra una baja proporción de cuidadores con sobrecarga. De igual forma, los pacientes presentan un nivel bajo de dependencia con una CVRS similar a la población general de referencia excepto en la función física (AU)

Introduction: A differential fact ambulatory peritoneal dialysis is the need for collaboration of a primary caregiver who is responsible for the patient’s treatment. This coupled with the chronic nature of this disease and possible dependence of the patient causes changes in the lifestyle of the primary caregiver being therefore a person exposed to overload. Objective: To identify the degree of overload of carers of patients in ambulatory peritoneal dialysis at the Reina Sofia Hospital in Cordoba and its relationship to quality of life and dependence of the patient. Patients and Methods: A descriptive and cross-sectional study. We studied 18 patients treated with continuous ambulatory peritoneal dialysis and their caregivers. We included all caregivers and patients who agreed to participate, prior informed consent. The SF-36 questionnaire was used to evaluate the quality of life of patients with test Zarit and questionnaire overload caregivers of patients in ambulatory peritoneal dialysis. With the latter, also it identified the level of dependence of the patient from the judgment of the caregiver. Results: Regarding the quality of life, there is a slight decrease in some of the dimensions of the general population for the same age. No overload found in most primary caregivers with any of the instruments used. A direct correlation was found between the two instruments. Regarding the level of dependence, 83% of patients were independent and 17% of patients were dependent. Conclusion: In view of these results, we can conclude that, at least in the sample is a low proportion of caregivers overload. Likewise, patients have a low level of dependence similar to the general population reference HRQOL except in physical function (AU)

Continuous ultrafiltration in acute decompensated heart failure: current issues and future directions.

Most patients hospitalized for acutely decompensated heart failure (ADHF) present with symptoms and signs of volume overload, which are also associated with high rates of death and re-hospitalization. Several studies have investigated the possible use of extracorporeal ultrafiltration in the management of ADHF, evaluating potential clinical benefits in terms of hospitalization and survival rates versus those of conventional diuretic therapy. Though ultrafiltration remains an extremely appealing therapeutic option for patients with AHDF, some of the most recent studies have reported conflicting results. Differences in the selection of study population, heterogeneity of the indications for the use of ultrafiltration, disparity in the ultrafiltration protocols, and high variability in the pharmacologic therapies used for the control group could explain some of these contradictory findings. The purpose of the present review is to provide an overview and an update on the mechanisms and clinical effects of ultrafiltration and on currently available evidence supporting its use in ADHF.

De dónde venimos y a dónde vamos en diálisis peritoneal: identificando barreras y estrategias de futuro / Where we come from and where we are going in terms of peritoneal dialysis: identifying barriers and strategies for the future

Pese a sus ya casi cuarenta años de historia y la mejora de la supervivencia tanto de la técnica como de los pacientes, la modalidad de diálisis peritoneal (DP) sigue siendo la menos utilizada. Tras un repaso histórico y un análisis de los datos actuales, analizamos los factores no médicos («el círculo vicioso») que contribuyen a la infrautilización de la DP: la formación deficiente de los especialistas, la falta de infraestructuras, las pequeñas unidades de DP, la falta de información a los pacientes, la proliferación de unidades de hemodiálisis, la escasez de consultas de enfermedad renal crónica avanzada o la forma de financiación de la diálisis. Y proponemos estrategias de futuro para mejorar y promocionar el uso y desarrollo de la DP (AU)

Despite the 40 years history, the comparable survival of Hemodialysis and Peritoneal Dialysis (PD), and the improved PD technique survival, the percentage of patients performing PD is low. After a short history review and data description, we analyze the many non-medical factors («the vicious circle») that contribute to the underutilization of PD: inadequate medical training, lack of infrastructures, small PD units, inadequate patient education for choice of dialysis modality, lack of multidisciplinary end-stage renal disease units, the proliferation of hemodialysis centers, or the trends in government reimbursement. Several of these factors are modifiable, and we propose future strategies to increase the use of PD (AU)

Worsening renal function in patients with acute decompensated heart failure treated with ultrafiltration: predictors and outcomes.

BACKGROUND: Ultrafiltration (UF) is used to treat patients with diuretic-resistant acute decompensated heart failure. The aim of this study was to identify predictors and the effect of worsening renal failure(WRF) on mortality in patients treated with UF. METHODS AND RESULTS: Based on changes in serum creatinine, 99 patients treated with UF were divided into WRF and control groups. Overall creatinine increased from 1.9 ± 0.7 to 1.2 ± 1.0 mg/dL (P!.001),and WRF developed in 41% of the subjects. The peak UF rate was higher in the WRF group in univariate analysis (174 ± 75 vs 144 ± 52 mL/h; P = .03). Based on multivariate analysis, aldosterone antagonist treatment (odds ratio [OR] 3.38, 95% confidence interval [CI] 1.17-13.46, P = .04), heart rate ≤65 beats/min (OR 6.03, 95% CI 1.48-48.42; P = .03), and E/E0 ≥ 15 (OR 3.78, 95% CI 1.26-17.55; P 5 .04) at hospital admission were associated with WRF. Patients with baseline glomerular filtration rate (GFR) ≤60mg/dL who developed WRF during UF had a 75% 1-year mortality rate. CONCLUSIONS: WRF occurred frequently during UF. Increased LV filling pressures, lower heart rate, and treatment with aldosterone antagonist at hospital admission can identify patients at increased risk for WRF. Patients with baseline GFR ≤60 mg/dL and WRF during UF have an extremely high 1-year mortality rate.

Worsening renal function in patients with acute decompensated heart failure treated with ultrafiltration: predictors and outcomes.

BACKGROUND: Ultrafiltration (UF) is used to treat patients with diuretic-resistant acute decompensated heart failure. The aim of this study was to identify predictors and the effect of worsening renal failure (WRF) on mortality in patients treated with UF. METHODS AND RESULTS: Based on changes in serum creatinine, 99 patients treated with UF were divided into WRF and control groups. Overall creatinine increased from 1.9 ± 9.7 to 2.2 ± 2.0 mg/dL (P < .001), and WRF developed in 41% of the subjects. The peak UF rate was higher in the WRF group in univariate analysis (174 ± 45 vs 144 ± 42 mL/h; P = .03). Based on multivariate analysis, aldosterone antagonist treatment (odds ratio [OR] 3.38, 95% confidence interval [CI] 1.17-13.46, P = .04), heart rate ≤65 beats/min (OR 6.03, 95% CI 1.48-48.42; P = .03), and E/E' ≥15 (OR 3.78, 95% CI 1.26-17.55; P = .04) at hospital admission were associated with WRF. Patients with baseline glomerular filtration rate (GFR) ≤60 mg/dL who developed WRF during UF had a 75% 1-year mortality rate. CONCLUSIONS: WRF occurred frequently during UF. Increased LV filling pressures, lower heart rate, and treatment with aldosterone antagonist at hospital admission can identify patients at increased risk for WRF. Patients with baseline GFR ≤60 mg/dL and WRF during UF have an extremely high 1-year mortality rate.

Recent advances in the monitoring and control of haemodynamic variables during haemodialysis: a review.

The human body possesses a unique set of organs that are responsible for providing homeostatic balance to the body's fluids. Of these, the kidneys regulate fluid and electrolyte balance in order to maintain the intracellular and extracellular fluid volumes and ion composition within tight limits. When kidneys fail to function normally, fluid is retained and several ions and solutes accumulate. The consequences may be life threatening. Many kidney failure patients rely on haemodialysis (HD) as a life sustaining therapy to remove the waste products and excess fluid from the circulating blood. HD is based on the principle of diffusion of solutes and ultrafiltration of fluid across a semi-permeable membrane. Fluid removal during HD results in relative hypovolaemia during which the stability of a patient relies on compensatory mechanisms to maintain blood pressure (BP). The major compensatory mechanisms include sympathetic nervous system activation of peripheral vasoconstriction together with modest heart rate acceleration to ensure the haemodynamic stability of the patient. Over the years, many monitoring tools have been developed in the hope of predicting intra-dialytic hypotensive episodes. Similarly many methods have been utilized to prevent dialysis-induced complications: ultrafiltration and dialysate sodium profiling, varying ultrafiltration based on frequent BP measurements, etc. This paper provides a comprehensive review of those monitoring and control tools. It starts with a brief introduction to human kidneys and dialysis for non-specialized readers. The paper then reviews the monitoring tools that have been applied to assess the physiological response of patients during HD. This is followed by control techniques used to prevent dialysis-induced complications.

Ultrafiltration is associated with fewer rehospitalizations than continuous diuretic infusion in patients with decompensated heart failure: results from UNLOAD.

BACKGROUND: Compare outcomes of ultrafiltration (UF) versus standard intravenous (IV) diuretics by continuous infusion or bolus injection in volume overloaded heart failure (HF) patients. In the Ultrafiltration versus Intravenous Diuretics for Patients Hospitalized for Acute Decompensated heart Failure (UNLOAD) study, UF produced greater fluid reduction and fewer HF rehospitalizations than IV diuretics in 200 hospitalized HF patients. Outcomes may be due to greater fluid removal, but UF removes more sodium/unit volume than diuretics. METHODS AND RESULTS: Outcomes of 100 patients randomized to UF were compared with those of patients randomized to standard IV diuretic therapy with continuous infusion (32) or bolus injections (68). Choice of diuretic therapy was by the treating physician. Forty-eight hour weight loss (kg): 5.0 +/- 3.1 UF, 3.6 +/- 3.5 continuous infusion, and 2.9 +/- 3.5 bolus diuretics (P = .001 UF versus bolus diuretic; P > .05 for the other comparisons). Net fluid loss (L): 4.6 +/- 2.6 UF, 3.9 +/- 2.7 continuous infusion, and 3.1 +/- 2.6 bolus diuretics (P < .001 UF versus bolus diuretic; P > .05 for the other comparisons). At 90 days, rehospitalizations plus unscheduled visits for HF/patient (rehospitalization equivalents) were fewer in UF group (0.65 +/- 1.36) than in continuous infusion (2.29 +/- 3.23; P = .016 versus UF) and bolus diuretics (1.31 +/- 1.87; P = .050 versus UF) groups. No serum creatinine differences occurred between groups up to 90 days. CONCLUSIONS: Despite similar fluid loss with UF and continuous diuretic infusion, fewer HF rehospitalizations equivalents occurred only with UF. Removal of isotonic fluid by UF compared with hypotonic urine by diuretics more effectively reduces total body sodium in congested HF patients.

Membrane processes and devices for separation of bioactive peptides.

In recent years, functional foods and nutraceuticals has attracted much attention, particularly for their impact on human health and prevention of certain diseases. Consequently, the production and properties of bioactive peptides has received an increasing scientific interest over the past few years. Considering that most functional peptides are present in complex matrices containing a large number of hydrolyzed protein fractions, their separation and purification are required. Conventional pressure-driven processes can be used for amino acids and peptides separation but are limited by their fouling problems and their low selectivity when separating similar sized biomolecules. To improve the separation efficiency, an external electric field was applied during pressure-driven filtration. However, the pressure gradient brings about the accumulation of peptides at the nearby membrane surface and affects the membrane transport selectivity. Processes combining an electrical field as a driving force to porous membranes have been developed for the separation of biopeptides to obtain better purified products. Compounds of higher molecular weights than the membrane cut-off can be separated. The first trials were carried-out to perform the separation of amino acids and peptides with a filtration module specially designed and using one ultrafiltration membrane. More recently, electrodialysis with ultrafiltration membranes has been developed to fractionate simultaneously acidic and basic peptides, using a conventional electrodialysis cell, in which some ion exchange membranes are replaced by ultrafiltration ones. The perspectives in this field will be the understanding of the interactions of peptides and membrane as well as the development of new membrane materials limitating or increasing these interactions to improve the selectivity and the yield of production of specific peptides. This review article also discusses recent patents related to bioactive peptides.

Ultrafiltration for the management of acute decompensated heart failure.

Heart failure is a major public health problem and is increasing in incidence throughout the industrialized world. Despite recent advances in pharmacotherapy, the overall mortality remains high and largely unchanged. Ultrafiltration has received increased attention in the treatment of acute decompensated congestive heart failure, and recent clinical trials suggest its usefulness in removing volume while preserving renal function. This review will focus on the background of ultrafiltration in the treatment of acute decompensated heart failure as well as the current evidence regarding its efficacy and safety.

Outcomes of volume-overloaded cardiovascular patients treated with ultrafiltration.

BACKGROUND: Ultrafiltration (UF) can rapidly and predictably remove extracellular and intravascular fluid volume. To date, assessment of UF in patients with cardiovascular disease has been confined to short- and medium-term studies in patients with a principal diagnosis of acute heart failure. METHODS: In-hospital and long-term outcomes were reviewed from consecutive patients with cardiovascular disorders and recognized pulmonary and systemic volume overload treated with a simplified UF system with the capability for peripheral venovenous access. Trained abstractors reviewed both paper and electronic medical records. Patients with a principal diagnosis of heart failure versus other primary hospital discharge diagnoses were identified according to International Classification of Diseases, 9th Revision standards by independent coders. RESULTS: For a period of 43 months, 100 patients (76 male/24 female, 65 +/- 14.0 years of age, systolic dysfunction 64%) were treated with UF during 130 hospitalizations. Baseline systolic blood pressure was 119 +/- 23 mm Hg. Before UF, 53% were receiving intravenous vasoactive therapy. By using UF, 7.1 +/- 3.9 L of ultrafiltrate were removed during 2.0 +/- 1.2 treatments per hospitalization. Baseline creatinine was 1.8 +/- 0.8 and 1.9 +/- 1.2 (not significant) at discharge. Of the 15 in-hospital deaths, 14 occurred during the initial hospitalization. Left ventricular dysfunction was related to 13 (87%) of the 15 deaths; no deaths were related to UF use. In hospitalizations with a principal diagnosis of heart failure (n = 79), in-hospital mortality was 7.6% compared with an ADHERE risk tree estimated mortality of 7.5%. Multivariate logistic regression identified a trend for decreased systolic blood pressure to predict patient initial hospitalization mortality (P = .06). Kaplan-Meier survivals for all patients were 71% at 1 year and 67% at 2 years. Cox regression found decreased systolic blood pressure as a predictor of long-term mortality (P = .025). Total volume of ultrafiltrate removed, ejection fraction, history of coronary artery disease, creatinine clearance, gender, age, and principal diagnosis of heart failure were not significantly associated with long-term mortality. CONCLUSION: This series extends the spectrum of patients previously reported to be treated with UF. Despite marked volume overload, UF-treated patients with a principal diagnosis of heart failure had inpatient outcomes similar to the ADHERE registry. UF should be considered for a broad range of patients who present with volume overload.

Bioseparation in antibody manufacturing: the good, the bad and the ugly.

Improvements in upstream production have boosted productivity in the biomanufacturing industry, but this is leading to bottlenecks in downstream processing as current technology platforms reach their limits of throughput and scalability. Although chromatography remains an indispensible component of downstream processing due to its simplicity and high resolving power (The Good), there is virtually no economy of scale effect so more product translates almost linearly into greater production costs. Bind-and-elute processes (such as the initial capture step in antibody manufacturing) are volume-driven and therefore have knock-on effects that impact on the entire production facility since the space required for preparation, storage, and cleaning steps has to be similarly adapted (The Bad). During long-term operations with multiple cycles, thorough cleaning is necessary to prevent progressive fouling and microbial contamination (The Ugly). Innovative solutions are required, which may include revisiting simpler and less expensive separation technologies, the use of disposable modules, and the integration of improved processes that are scalable to cope with increased demands. Among the alternatives that have been put forward, membrane adsorbers are beginning to make a real impact on the industry, particularly for flow-through applications such as polishing and viral clearance.

Advances in primary recovery: centrifugation and membrane technology.

Significant and continual improvements in upstream processing for biologics have resulted in challenges for downstream processing, both primary recovery and purification. Given the high cell densities achievable in both microbial and mammalian cell culture processes, primary recovery can be a significant bottleneck in both clinical and commercial manufacturing. The combination of increased product titer and low viability leads to significant relative increases in the levels of process impurities such as lipids, intracellular proteins and nucleic acid versus the product. In addition, cell culture media components such as soy and yeast hydrolysates have been widely applied to achieve the cell culture densities needed for higher titers. Many of the process impurities can be negatively charged at harvest pH and can form colloids during the cell culture and harvest processes. The wide size distribution of these particles and the potential for additional particles to be generated by shear forces within a centrifuge may result in insufficient clarification to prevent fouling of subsequent filters. The other residual process impurities can lead to precipitation and increased turbidity during processing and even interference with the performance of the capturing chromatographic step. Primary recovery also poses significant challenges owing to the necessity to execute in an expedient manner to minimize both product degradation and bioburden concerns. Both microfiltration and centrifugation coupled with depth filtration have been employed successfully as primary recovery processing steps. Advances in the design and application of membrane technology for microfiltration and dead-end filtration have contributed to significant improvements in process performance and integration, in some cases allowing for a combination of multiple unit operations in a given step. Although these advances have increased productivity and reliability, the net result is that optimization of primary recovery processes has become substantially more complicated. Ironically, the application of classical chemical engineering approaches to overcome issues in primary recovery and purification (e.g., turbidity and trace impurity removal) are just recently gaining attention. Some of these techniques (e.g., membrane cascades, pretreatment, precipitation, and the use of affinity tags) are now seen almost as disruptive technologies. This paper will review the current and potential future state of research on primary recovery, including relevant papers presented at the 234th American Chemical Society (ACS) National Meeting in Boston.

Alternatives to chromatographic separations.

Up to now, the productivity of mammalian cell culture has been perceived as limiting the productivity of the industrial manufacture of therapeutic monoclonal antibodies. Dramatic improvements in cell culture performance have changed this picture, and the throughput of antibody purification processes is gaining increasing attention. Although chromatographic separations currently are the centerpiece of antibody purification, mostly due to their high resolving power, it becomes more and more apparent that there may be limitations at the very large scale. This review will discuss a number of alternatives to chromatographic antibody purification, with a particular emphasis on the ability to increase throughput and overcome traditional drawbacks of column chromatography. Specifically, precipitation, membrane chromatography, high-resolution ultrafiltration, crystallization, and high-pressure refolding will be evaluated as potential large scale unit operations for industrial antibody production.

Diseño de estrategias de optimización del volumen de reinfusión en hemodiafiltración en línea / Design of strategies to optimize the reinfusion volume in online haemodiafiltration

El diseño de algoritmos clínicos para la optimización del volumen de reinfusión en Hemodiafiltración en línea en 16 pacientes con insuficiencia renal crónica ha permitido incrementar este parámetro relacionado con la eficacia de la técnica, creando un lenguaje intermedio entre los diferentes especialistas que intervienen en el problema. Una de las consecuencias más importantes ha sido la disminución de la variabilidad de la práctica clínica y de enfermería a la hora de establecer en estos pacientes el QI óptimo. A consecuencia de estas estrategias, los resultados preliminaries se ajustan al objetivo propuesto (AU)

The design of clinical algorithms to optimize the volume of reinfusion in online haemodiafiltration in 16patients with chronic renal insufficiency has made it possible to increase this parameter related to the efficacy of the technique, creating an intermediate language among the different specialists involved in the problem. One of the most important consequences has been to reduce the variability of clinical and nursing practice in establishing the optimum QI in such patients. As a result of these strategies, the preliminary results respond to the proposed aim (AU)