bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Evaluation of Internal Hemodiafiltration (iHDF): A Diffusive-Convective Technique Performed with Internal Filtration Enhanced High-Flux Dialyzers
Authors: Lucchi L. , Fiore G.B. , Guadagni G. , Perrone S. , Malaguti V. , Caruso F. , Fumero R. , Albertazzi A.
Published: January 2018

Aim

Efficiency in removing middle molecules such as ß2-microglobulin (ß2-MG) is one of the main purposes of modern dialytic therapy. In order to achieve this, techniques requiring complex machines and substitution fluid have been developed over recent years. Alternatively, the internal filtration / back filtration phenomenon can be used. The recent development of a so-called “internal filtration enhanced dialyser” prompted us to compare the removal of ß2-MG together with other small molecules when the dialyser was used either in standard hemodiafiltration (HDF) or internal hemodiafiltration (iHDF).

Methods

Ten stable, anuric, hemodialysis (HD) patients treated by thrice weekly standard bicarbonate HD using low-flux synthetic membrane entered the study. A new high-flux polysulfone dialyser designed with the specific aim of enhancing internal filtration (BS-1.6 UL, 1.6 m2, Toray Industries) was used. Post dilution HDF (2.5 l/hour of substitution fluid, dialysate flow 500 ml/min) was compared with iHDF (dialysate flow 750 ml/min), with blood flow at 300 ml/min. Samples were obtained at the start and at the end of the session in order to measure the % removal of urea, creatinine, uric acid, phosphate and ß2-MG (corrected for total protein concentration). In addition, after 20 min of dialysis the clearances of the same molecules were measured. A mathematical model has been developed for the description of the hydrodynamic phenomena taking place within the dialyser and of fluid filtration across the membrane.

Results

No significant differences have been observed in removal rate switching from HDF to iHDF except for ß2-MG removal, which was slightly higher in HDF than in iHDF. Phosphate clearance is significantly higher than those obtained with creatinine in both HDF (p<0.005) and iHDF (p<0.01) modalities. The total convection calculated with the model is reduced with respect to HDF only by 24% (4100 ml/h vs. 5400 ml/h on the average).

Conclusions

iHDF is a high flux dialysis method, which, if performed with a dialyser designed to enhance internal filtration, obtains a much higher removal rate in comparison with dialysers in traditional high flux dialysis, as previously reported in the literature. Provided that the dialyser is used on a dialysis machine working with ultra pure dialysate and UF control, this dialyser line can perform reliable internal HDF without the need for replacement solution. Considering the narrow difference in performance observed between iHDF and HDF, and the increasing number (and age) of patients leading to higher dialysis costs, iHDF represents a cost-effective alternative to other diffusive-convective techniques.
Elimination of Linezolid by an in vitro Extracorporeal Circuit Model
Authors: Schroeder T.H. , Hansen M. , Stephan M. , Hoffmann E. , Unertl K. , Krueger W.A.
Published: January 2018

Linezolid is an oxazolidinone antibiotic with activity against important grampositive aerobic bacteria, including nosocomial pathogens. It is not known whether dosage adjustments are necessary in patients treated with continuous renal replacement therapies. This in vitro study was conducted to investigate the elimination of linezolid in an in vitro continuous hemo(dia)filtration model using different filter materials (polysulfone, polyacrylonitrile, polyamide), surface areas, and different modes of renal replacement therapies. Linezolid was measured using HPLC with UV-detection. No adsorption of linezolid to any of the tested membranes was detected. Recovery of linezolid in the ultrafiltrate was 98.2 ± 10.5% in the filtration mode. During dialysis, recovery was significantly less (87.6 ± 16.1%; p = 0.02). Linezolid elimination was not altered by filter size, when polysulfone filters with surface areas of 0.7 m2 and 1.3 m2 were tested. In conclusion, the dosage recommendations for linezolid are independent of the filter materials. However, the elimination is significantly higher during hemofiltration compared to dialysis.
Endotoxin Removal from Whole Blood by a Novel Adsorption Resin: Efficiency and Hemocompatibility
Authors: Amoureux M.-C. , Rajapakse N. , Hegyi E. , Le D. , Grandics P. , Szathmary S.
Published: January 2018

The structural component of Gram- bacteria, endotoxin (ET), induces the release of endogenous mediators of sepsis. Attempts to remove these downstream molecules in vivo, have not improved survival. However, extracorporeal strategies such as continuous renal replacement therapy or therapeutic plasmapheresis have shown benefit. We are presenting an affinity-based extracorporeal technology for the removal of ET from whole blood. The small-scale device contains an adsorbent that removed 75% of ET present in whole blood. This affinity resin displayed good hemocompatibility regarding the coagulation pathway. Minimal platelet, neutrophil and complement activation were observed. There was also no evidence of consumption of coagulation factors or cell loss. In as much as ET participates in both the inflammatory and coagulation abnormalities in sepsis, this method represents an efficient and hemocompatible way to remove ET from whole blood, which, in an extracorporeal setting, may improve the outcome of sepsis.
Poly(2-Hydroxyethyl Methacrylate) Biomimetic Coating to Improve Osseointegration of a PMMA/HA/Glass Composite Implant: In vivo Mechanical and Histomorphometric Assessments
Authors: Giavaresi G. , Branda F. , Causa F. , Luciani G. , Fini M. , Aldini N. Nicoli , Rimondini L. , Ambrosio L. , Giardino R.
Published: January 2018

Bone implants must simultaneously satisfy many requirements, even though the surface properties remain a crucial aspect in osseointegration success. Since a single material with a uniform structure cannot satisfy all of these requirements, composite materials specifically designed for orthopedic or dental implant application should be envisaged. Two poly(methyl-methacrylate)/hydroxyapatite composites reinforced by E-glass fibres, uncoated (PMMA/HA/Glass) and poly(2-hydroxyethyl methacrylate) (PMMA/HA/Glass+pHEMA) coated by the biomimetic method, were mechanically (push-out test) and histomorphometrically (Affinity Index, AI) investigated in an in vivo rabbit model. Cylindrical implants (ø 2 mm × 5 mm length) were inserted into rabbit femoral cortical (mid-diaphysis) and cancellous (distal epiphysis) bone, under general anesthesia. The highest values of push-out force and ultimate shear strength were observed for the PMMA/HA/Glass at 12 weeks, which significantly (p < 0.001) differed from those of PMMA/HA/Glass+pHEMA at the same experimental time and from those of PMMA/HA/Glass at 4 weeks. At both experimental times, significantly (p < 0.0005) lower values of AI were observed in the PMMA/HA/Glass+pHEMA versus PMMA/HA/Glass (distal femoral epiphysis: 4 weeks = 33%; 12 weeks = 19%; femoral diaphysis: 4 weeks = 15%; 12 weeks = 11%). The good mechanical and histomorphometric results obtained with PMMA/HA/Glass should be followed by further evaluation of bone remodeling processes and mechanical strength around loaded PMMA/HA/Glass implants at longer experimental times. Finally, the biomimetic method applied to pHEMA needs to be further investigated in order to improve the positive effect of SBF on pHEMA and to enhance the coating adhesion.
Bilirubin-Adsorption in 23 Critically Ill Patients with Liver Failure
Authors: Senf R. , Klingel R. , Kurz S. , Tullius S. , Sauer I. , Frei U. , Schindler R.
Published: January 2018

Purpose

Previous studies suggest that high levels of bilirubin exert cytotoxic, neurotoxic and encephalopathic effects that themselves may lead to further deterioration of liver function and multiorgan failure. Although extracorporeal BA is not a causal therapy, there are case reports of clinical benefits of BA. The present retrospective study investigated the clinical utility and effectiveness of BA in 23 patients with liver failure.

Methods

Twenty-three patients (61±11 years) with excessive hyperbilirubinemia (>25 mg/dL) after liver transplantation (n=7), partial liver resection (n=12) and others (n=4) were treated with BA (3.6 liters plasma per BA, BR350, Asahi) and followed for 45±8 days.

Results

A mean of 6.6 treatments (3–16) were performed per patient. On average, a single BA treatment reduced bilirubin-levels from 31±12 to 23.7±9 mg/dL (p<0.001). Levels of bile acid were reduced from 41.8±6 to 33.5±5 mg/dL. The 30-day mortality was 50%. BA was able to halt and stabilize the progressive increase in bilirubin levels in all patients. In contrast to survivors, non-survivors were characterized by a repeated rapid rise in bilirubin levels after cessation of BA treatment.

Conclusions

BA is able to stabilize or decrease bilirubin levels in patients with liver failure. Our experience suggests that BA is a safe and promising short-term treatment option for patients with acute deterioration of hepatic function.
Cardiac Calcium Evaluation in Hemodialysis Patients with Multisection Spiral Computed Tomography
Authors: Splendiani G. , Morosetti M. , Manni M. , Jankovic L. , Naticchia A. , Sturniolo A. , Tullio T , Balducci A. , Coen G.
Published: January 2018

Aim

The aim of this study is cardiac calcium content evaluation in hemodialysis patients by a new technique, based on ultrafast multisection CT (MTC).

Methods

The study was carried out on 30 HD patients, 14F and 16 M, average age 57.7±13.9 years, average HD age 57.3±47.4 months. The intact PTH levels were 625.4±571 pg/mL. Serum calcium, phosphate and CaxP product were 9.75±0.84 mg/mL, 6.21±1.01 mg/dL and 60.2±10.7 mg2/dL2, respectively.

Results

The values obtained with the MTC technique were reported in terms of Agatson scores. Score values frankly in the pathologic range (>100) were found in 24 patients (80%). Correlation analysis has shown positive and significant correlation coefficients of the score with patients’ age (p=0.003), serum calcium (p=0.012), CaxP (p=0.015), iPTH (=0.049), and borderline, to HD age (p=0.06).

Conclusion

Risk factors for cardiac calcification are mainly age, degree of hyperparathyroidism, increased CaxP and serum calcium levels. A control of calcium phosphate parameters in hemodialysis patients seems to be mandatory to avoid increased severity of coronary artery disease.
Investigation of a New Microcapsule Membrane Combining Alginate, Chitosan, Polyethylene Glycol and Poly-L-Lysine for Cell Transplantation Applications
Authors: Haque T. , Chen H. , Ouyang W. , Martoni C. , Lawuyi B. , Urbanska A. , Prakash S.
Published: January 2018

Microencapsulation of living cells may serve as an alternative therapy for patients requiring organ transplants. One of the limiting factors in the progress of such therapy is attaining a biocompatible and mechanically stable polymer. The current study investigates the potential of a novel membrane combining alginate, chitosan, polyethylene glycol (PEG) and poly-L-lysine (PLL) with the objective of proposing a membrane suitable for cell entrapment that may overcome some of the shortcomings of the widely studied alginate-poly-L-lysine-alginate (APA) capsules. The novel microcapsule was formulated using a 1.5% alginate solution coated with 0.05% chitosan, 0.1% PEG and 0.05% poly-L-lysine with a final layer of 0.1% alginate. Microcapsules having a diameter of 450 ± 30 μm were prepared. Upon citrate treatment, the membrane remained intact and retained its spherical structure. The membrane was able to support liver cell proliferation and the encapsulated cells were capable of secreting proteins. The study demonstrated that the new membrane can be used for cell entrapment. However, further investigations are needed to assess its potential for long term transplantation and usage in the development of bioartificial organs.
Structural Changes in Pericardium Tissue Modified with Tannic Acid
Authors: Cwalina B. , Turek A. , Nozynski J. , Jastrzebska M. , Nawrat Z.
Published: January 2018

Introduction

Structural modification of proteins, mainly collagen in connective tissues, is important in the manufacture of tissue-derived biomaterials. Natural compounds like genipin or tannic acid (TA) have been proposed instead of glutaraldehyde which shows cytotoxic effects on the processed tissue. Furthermore, calcification of glutaraldehyde-treated tissue limits the functional lifetime of bioprostheses. TA is known to form numerous hydrogen bonds with proteins. The purpose of our study was to investigate structural changes in porcine pericardium upon chemical modification with tannic acid.

Methods

Porcine pericardium tissue (PP) was soaked in 2% TA for 4, 24 or 48 hours. Changes in tissue structure were studied using electrophoresis (SDS-PAGE) and histological examination. Structural stability of PP tissue was evaluated by SDS/NaCl extraction method and enzymatic digestion with pancreatin.

Results

TA-modification of PP caused a time-dependent decrease in the number of peptides extracted from tissue. Microscopic studies revealed no significant morphological differences between native and TA-modified tissues, except for the native pancreatin-digested tissue where lack of both cells and low molecular peptides was observed.

Conclusion

Modification of PP with TA causes the structural changes leading to an increase in the tissue resistance to SDS/NaCl extraction and enzymatic digestion, providing experimental evidence for the higher structural stability of TA-treated tissue.
Materials Characterization of Explanted Mechanical Heart Valves and Comparison to Patients’ Clinical Data
Authors: Farè S. , Brunella M.F. , Bruschi G. , Cigada A. , Vitali E.
Published: January 2018

In the present study, twelve explanted mechanical heart valves (MHVs) with pyrolitic carbon tilting disc and 14 bileaflet MHVs were analyzed to investigate the effects of material properties on valve performance and patients’ general health conditions. Optical and scanning electron microscopy was used to investigate material imperfections, wear patterns or damages to housing and occluder components. All analyzed tilting disc valves exhibited wear effects, particularly due to abrasion and impact to both disc and housing. Wear of pyrolitic carbon disc and housing did not influence their in vivo performance. In the bileaflet MHVs, breakaway of the pyrolitic carbon coating sometimes caused malfunctioning and required surgical retrieval of the valve. In all cases, occurrence of clinical symptoms was more likely when wear effects were located in critical areas. The study supports a correlation between the properties of the MHVs material and patients’ symptoms.
Combining SPECT Medical Imaging and Computational Fluid Dynamics for Analyzing Blood and Dialysate Flow in Hemodialyzers
Authors: Eloot S. , D'asseler Y. , De Bondt P. , Verdonck P.
Published: January 2018

For a better insight in dialyzer efficiency with respect to local mass transport in a low flux dialyzer (Fresenius F6HPS), blood and dialysate flow distributions were visualized with computational fluid dynamic (CFD) simulations, which were validated with single photon emission computed tomography (SPECT) imaging. To visualize blood-side flow while avoiding transport through the fiber membrane, a bolus of 99m-Technetium labeled MAA (Macro Aggregated Albumin) was injected in the flow using an electronic valve. Water was used to simulate blood, but flow rate was adjusted according to laws of dynamic similarity to account for the viscosity difference (factor 2.75). For the visualization of dialysate flow, a bolus of 99m-Technetium labeled DMSA (Dimercaptosuccinic Acid) was injected, while pressurized air in the blood compartment avoided transmembrane flow. For each test series, 3D acquisitions were made on a two respectively three-headed SPECT camera. By evaluating the images at different time steps, dynamic 3D intensity plots were obtained, which were further used to derive local flow velocities. Additionally, three-dimensional CFD models were developed for simulating the overall blood and dialysate flow, respectively. In both models, the whole fiber compartment was defined as a porous medium with overall axial and radial permeability derived theoretically and from in vitro tests. With the imaging as well as with the computational technique, a homogeneous blood flow distribution was found, while vortices and fluid stagnation were observed in the dialyzer inlet manifold. The non-homogeneous dialysate distribution, as found with SPECT imaging, implies the occurrence of non-efficient sites with respect to mass transfer. The discrepancy between the dialysate results of both techniques indicated that the assumption of a constant fiber bundle permeability in the CFD model was too optimistic. In conclusion, medical imaging techniques like SPECT are very helpful to validate CFD models, which can be further applied for dialyzer design and optimization.
Development of a Hybrid (numerical-hydraulic) Circulatory Model: Prototype Testing and Its Response to IABP Assistance
Authors: Ferrari G. , Kozarski M. , De Lazzari C. , Ska K. Górczyń , Tosti G. , Darowski M.
Published: January 2018

Merging numerical and physical models of the circulation makes it possible to develop a new class of circulatory models defined as hybrid. This solution reduces the costs, enhances the flexibility and opens the way to many applications ranging from research to education and heart assist devices testing. In the prototype described in this paper, a hydraulic model of systemic arterial tree is connected to a lumped parameters numerical model including pulmonary circulation and the remaining parts of systemic circulation. The hydraulic model consists of a characteristic resistance, of a silicon rubber tube to allow the insertion of an Intra-Aortic Balloon Pump (IABP) and of a lumped parameters compliance. Two electro-hydraulic interfaces, realized by means of gear pumps driven by DC motors, connect the numerical section with both terminals of the hydraulic section.

The lumped parameters numerical model and the control system (including analog to digital and digital to analog converters) are developed in LabVIEW™ environment. The behavior of the model is analyzed by means of the ventricular pressure-volume loops and the time courses of arterial and ventricular pressures and flows in different circulatory conditions. A simulated pathological condition was set to test the IABP and verify the response of the system to this type of mechanical circulatory assistance.

The results show that the model can represent hemodynamic relationships in different ventricular and circulatory conditions and is able to react to the IABP assistance.
A Mathematical Model for the Prediction of Solute Kinetics, Osmolarity and Fluid Volume Changes during Hemodiafiltration with On-Line Regeneration of Ultrafiltrate (HFR)
Authors: Ursino M. , Colì L. , Magosso E. , Capriotti P. , Fiorenzi A. , Baroni P. , Stefoni S.
Published: January 2018

Hemodiafiltration with on-line regeneration of ultrafiltrate (HFR) is a technique indicated for the treatment of dialysis patients affected by inflammatory syndrome and malnutrition. In the present work, a mathematical model, which describes intradialytic fluid and solute kinetics during standard diffusive dialysis, has been adapted to analyze solutes and fluid dynamics during HFR. The model is an improved version of our previous ones, and represents a good compromise between simplicity and reliability. It considers the intradialytic kinetics of sodium, potassium and urea, and two body fluid compartments: intracellular and extracellular. Moreover, the model includes simple equations to predict the intradialytic time pattern of osmolarity.

The model has been experimentally validated by using 9 HFR sessions on 9 patients (one per each patient), comparing the time course of plasma solutes and osmolarity measured every 30 minutes during HFR, with those predicted by the model. Predictions are performed a priori, i.e., without any parameter adjustment, but just starting from knowledge of a few quantities (plasma sodium, potassium, urea, osmolarity and body weight) at the beginning of the session.

The average deviations between model and real data (sodium: 1.9 mEq/L; potassium: 0.32 mEq/L; urea: 1.04 mmol/L; osmolarity: 5.02 mosm/L) are of the same order as measurement errors and similar to those obtained using our previous models in standard and profiled hemodialysis. Moreover, the prediction on sodium concentration only scarcely worsens (from 1.9 to 2.02 mEq/L) if default values are used for the initial value of other solutes in blood (i.e., if the algorithm uses only initial body weight and initial sodium concentration in plasma).

The results confirm the good predictive capacity of the model in HFR, and suggest its possible innovative use to optimize sodium balance in HFR, from knowledge of only the sodium concentration in the ultrafiltrate. (Int J Artif Organs 2006; 29: 1031–41)
Mobile Telecare System for Intensive Insulin Treatment and Patient Education. First Applications for Newly Diagnosed Type 1 Diabetic Patients
Authors: Ładyżyński P. , WÓJcicki J.M. , Krzymień J. , Foltyński P. , Migalska-Musiał K. , Tracz M. , Karnafel W.
Published: January 2018

The aim of the work was to develop and to evaluate the clinical efficiency of a mobile telecare system implementing teleconsultations based on the continuous transmission of patient-collected data directly to the physician and to the clinic.

The developed TeleMed system consists of the patients' and the diabetologist's mobile units, the diabetologist's clinic and home workstations and the clinical server. The evaluation of the system was performed on a group of 13 newly diagnosed type 1 diabetic patients, during a single-arm study with 3-days run-in period, including a one-day intensive educational program, and 3-week study period, when the intensive insulin treatment was conducted without visits of patients to the clinic. The MBG dropped from 7.2 ± 1.7 mmol/L before the study to 6.1 ± 1.0 mmol/L in the third week of the study (P = 0.02) and the J-index from 30.2±19.2 to 19.7±7.7 (P = 0.04). Hemoglobin A1c decreased from 11.8 ± 3.3% to 8.6 ± 1.2% (P = 0.0002) in one month. The total daily insulin dose declined from 39.9 ± 8.5 U to 20.0 ± 9.6 U (P = 0.000006). The number of hypoglycemia episodes per patient per day decreased by 66% (P = 0.08) and the number of hyperglycemia episodes was reduced by 47% (P < 0.0001).

The TeleMed facilitates not only efficient realization of the intensive insulin treatment but also successful remote patient training and education. No formal patient satisfaction study was done. However, some of the findings indicate that the application of the developed system increases patient self-confidence and quality of life. (Int J Artif Organs 2006; 29: 1074–81)
Bioactive Hydrogel-Filament Scaffolds for Nerve Repair and Regeneration
Authors: Newman K.D. , McLaughlin C.R. , Carlsson D. , Li F. , Liu Y. , Griffith M.
Published: January 2018

The design of novel biomaterials is crucial for the advancement of tissue engineering in nerve regeneration. In this study we developed and evaluated novel biosynthetic scaffolds comprising collagen crosslinked with a terpolymer of poly(N-isopropylacrylamide) (PNiPAAm) as conduits for nerve growth. These collagen-terpolymer (collagen-TERP) scaffolds grafted with the laminin pentapeptide YIGSR were previously used as corneal substitutes in pigs and demonstrated enhanced nerve regeneration compared to allografts. The purpose of this project was to enhance neuronal growth on the collagen-TERP scaffolds through the incorporation of supporting fibers. Neuronal growth on these matrices was assessed in vitro using isolated dorsal root ganglia as a nerve source. Statistical significance was assessed using a one-way ANOVA. The incorporation of fibers into the collagen-TERP scaffolds produced a significant increase in neurite extension (p<0.05). The growth habit of the nerves varied with the type of fiber and included directional growth of the neurites along the surface of certain fiber types. Furthermore, the presence of fibers in the collagen-TERP scaffolds appeared to influence neurite morphology and function; neurites grown on fibers-incorporated collagen-TERP scaffolds expressed higher levels of Na channels compared to the scaffolds without fiber. Overall, our results suggest that incorporation of supporting fibers enhanced neurite outgrowth and that surface properties of the scaffold play an important role in promoting and guiding nerve regeneration. More importantly, this study demonstrates the potential value of tissue engineered collagen-TERP hybrid scaffolds as conduits in peripheral nerve repair.
Long-Term Peritoneal Dialysis Experience in Portugal
Authors: Rodrigues A.S. , Matos C.B. , Silva F. , Fonseca I. , Nogueira C. , Santos J. , Silva A.S. , Cabrita A.
Published: January 2018

Peritoneal dialysis (PD) penetration varies widely. Since the beginning of this therapy, indications have changed and outcomes have improved. In Portugal, PD still remains clearly underutilized.

The results of a 20 year PD programme were evaluated: 312 cumulative patients, 48±16 years, 27% >60 years old, 27% diabetic, 59% with prior hemodialysis (HD). The main reason for admission was vascular access failure (48.7%). Admission due to patient preference has increased significantly between first and second decades of the programme (33% vs 47% (P<0.001)); 98 patients (31.4%) were treated with automated PD but this prescription increased to 43% of the active patients.

A total of 376 Tenckhoff catheters were surgically implanted, recently by the Popovich-Moncrief technique (77 catheters): the cumulative survival was 82%, 64% and 50% at 1, 3 and 5 years, respectively. A better catheter survival was found in the last decade (85.7%, 69.6%, 54.8% versus 77.3%, 55.5%, 40.2%, at 1, 3 and 5 years, respectively (P=0.007).

The patient and technique cumulative survivals were 91, 74, 55% and 85, 67, 41%, at 1, 3, and 5 years, respectively.

The main drop-out was to hemodialysis (35.8%), followed by death (23.7%), and transplantation (21.5%). Peritonitis and access-related infections caused 35% of the transfer to HD. Cardiovascular events caused 58% of deaths. The median PD retention was 35.5 months. The rate of peritonitis has decreased to one episode /30 patient months. Hospital admission has also decreased to 4.8 days/patient year.

This is a first report on long-term PD experience in Portugal. It has been an effective modality of renal replacement therapy, reflected by the growing patient preference in our PD programme. Experience, knowledge and new technical solutions have improved the outcomes.
Autopsy Findings in Patients on Postcardiotomy Extracorporeal Membrane Oxygenation (ECMO)
Authors: Rastan A.J. , Lachmann N. , Walther T. , Doll N. , Gradistanac T. , Gommert J.F. , Lehmann S. , Wittekind C. , Mohr F.W.
Published: January 2018

Objectives

To assess the clinical sensitivity of causes of death, concomitant diseases and postoperative complications including thromboembolic events in ECMO patients. Methods: Between January 2000 and December 2004 154/202 patients (76.2%) died after postcardiotomy ECMO circulatory support. Autopsy was performed in 78 (50.6%) consecutive patients. Clinical and post-mortem data were prospectively recorded and compared concerning causes of death and postoperative complications including venous and arterial thromboembolisms and significant comorbidities.

Results

Mean age was 62.1±11.3 years, ejection fraction was 43.4±17.3%. 39.7% were emergency operations including acute coronary syndrome in 25.6% and preoperative cardiogenic shock in 28.2%. Successful ECMO weaning rate was 43.6%. Mean postoperative survival was 11.3 days. Premortem unknown concomitant diseases were found in 63 patients (80.8%) with clinical relevance in 9 patients (11.5%). Clinically unrecognized postoperative complications were found in 59 patients (75.6%) including acute cerebral infarction (n=7), acute bowel ischemia (1), intestinal perforation (3), pneumonia (4), venous thrombus formation (25) and systemic thromboembolic events (24). Clinically based causes of death were cardiac in 62.8%, multi-organ failure in 10.3%, cerebral in 5.1%, respiratory in 10.3%, fatal pulmonary embolism in 2.6%, technical in 5.1%, and others in 3.8%. Unexpected causes of death were found by autopsy in 22 patients (28.2%) including myocardial infarction (n=5), acute heart failure (4), fatal pulmonary embolism (2), pneumonia (2), ARDS (1), lung bleeding (1), fatal cerebrovascular event (4) and multiorgan failure (3).

Conclusions

In ECMO patients major discrepancies between clinical and post-mortem examination were found. The true incidence of thromboembolic events is highly underestimated by clinical evaluation.
Autonomously Contracting Human Cardiomyocytes Generated from Adult Pancreatic Stem Cells and Enhanced in Co-Cultures with Myocardial Biopsies
Authors: Guldner N.W. , Kajahn J. , Klinger M. , Sievers H.-H. , Kruse C.
Published: January 2018

Myocardial regeneration with artificially applied cardiomyocytes is emerging as a promising issue of significant scientific and clinical impact. Nevertheless the source of cells for human cardiomyocyte differentiation especially from adult tissue is still unclear. We hypothesized that human pancreatic stem cells may differentiate into cardiomyocyte-like cells and may increase in number when co-cultured with myocardial tissue.

Adult stem cells were harvested from pancreatic tissue of patients undergoing operative procedures including the pancreas. The cells were selected, cultured and passaged. To promote self-differentiation into cardiomyocytes, human pancreatic stem cells were co-cultered with biopsies of human myocardium. After co-culture and breeding, cells were phenotyped as well with respect to RNA, protein and cardiomyocyte specificity at the electron-microscopic level.

Pancreatic stem cells have already differentiated spontaneously into cardiomyocyte-like cells performing netlike cell clusters with rare but distinct multilocular cellular autonomous contractions with a frequency of about 20 beats per minute. The number of contracting areas however could be enhanced by co-culture with human myocardial biopsies. On RNA and protein levels as well as in electron-microscopy evidence for cardiomyocyte specificity is shown.

To the best of our knowledge this is the first report demonstrating the feasibility of generating autonomously contracting cardiomyocyte-like cells from adult human pancreatic stem cells and their enhancement by myocardial co-culture. This procedure might prove to be an alternative source and method for myocardial regenerative medicine.
Hepatitis C Virus Infection in Hemodialyzed Patients
Authors: Vecchi M. LI , La Spada E. , Vecchi V. LI , Montalto G.
Published: January 2018

In spite of our present improved knowledge of the epidemiology and pathways of contamination of the hepatitis C virus (HCV), infection still remains a public health problem. One category of patients who have suffered greatly from the consequences of HCV infection is certainly that of hemodialysis patients. In the past, in fact, their need for transfusions exposed these patients to infection and, as a result, subjects on dialysis for over 15 years are today paying the price for those inevitable transfusions, as the virus and its pathways of contagion were unknown then. However, still today, albeit at a much lower prevalence, even subjects with a shorter dialysis age present a higher prevalence of anti-HCV than the general population, suggesting that other factors of contamination than the classical ones contribute to keeping this prevalence high. Its clinical course is generally asymptomatic and the biological and virological progression of the disease is quite particular and apparently benign. The mortality rate of infected patients is higher than in non-infected subjects and this is not only due to the liver disease itself but also to cardiovascular disorders.

Even anti-viral therapy, after its first timid steps, is now routinely used in patients with a certain degree of liver damage and kidney transplant candidates. The appropriate use of pegylated interferons is expected to improve the percentage of eradication and limit side effects, in parallel with what has been observed in non-dialysis patients. Ribavirin, however, is at present contraindicated due to its toxic effects on red blood cells as hemoglobin content could be dangerously reduced in these patients.
Ultrafiltration Rate as a Dose Surrogate in Pre-Dilution Hemofiltration
Authors: Huang Z. , Letteri J.J. , Clark W.R. , Zhang W. , Gao D. , Ronco C.
Published: January 2018

For critically ill patients treated with continuous hemofiltration (HF), doses recently shown to improve survival can usually be achieved only in the pre-dilution mode. However, use of the pre-dilution mode results in reduced treatment efficiency, relative to post-dilution at the same ultrafiltration rate (Qf) and blood flow rate (Qb). The objective of this study is to determine the effect of Qf on removal parameters for solutes over a wide molecular weight spectrum in pre-dilution HF. Experiments were performed in an isovolemic, plasma-based pre-dilution system with Qb=200 ml/min. Removal parameters were measured for a 1.2 m2 polysulfone hemofilter (HF1200, Minntech) at Qf values of 20, 40, and 60 ml/min, corresponding to 17, 34 and 51 ml/h/kg for a 70 kg patient (N=3 hemofilters for each Qf). Clearance of urea and creatinine (small solute surrogates) was derived from plasma and ultrafiltrate concentrations at 30, 60, 120, 180, and 240 min while clearance of vancomycin and inulin (middle molecule surrogates) was estimated from changes in plasma concentrations over time. In addition, the sieving coefficient (SC) of vancomycin and inulin was measured at the same time points and at baseline (T=0 min). Our findings indicate pre-dilution had a predictable effect on clearance for each solute, as clearance increased linearly with Qf. Sieving coefficient values were not significantly influenced by either Qf or time and the equivalence of SC values in the middle molecule range suggest attenuation of secondary membrane effects. These data indicate filter performance can largely be preserved despite high Qf values by use of pre-dilution. Moreover, Qf appears to be a reasonable dose surrogate in pre-dilution HF.
Correlation between HSP-72 Expression and IL-8 Secretion in Human Mesothelial Cells
Authors: Bender T. O. , Riesenhuber A. , Endemann M. , Herkner K. , Witowski J. , JöRres A. , Aufricht C.
Published: January 2018

Background

Cytotoxicity of peritoneal dialysis fluid (PDF) and peritoneal inflammation are currently regarded as the two major culprits for chronic mesothelial injury and peritoneal membrane failure. In this study, we correlated induction of HSP-72, as a marker of the cellular stress response, to secretion of IL-8, as a marker for pro-inflammatory cytokines, in mesothelial cells upon sublethal PDF exposure.

Methods

Primary omental cell cultures of human mesothelial cells were subjected to sublethal PDF exposure times (CAPD2, Fresenius, Germany). At the end of a 24 hour recovery period, induction of HSP-72 in the cell homogenate and IL-8 secretion in the supernatant was assessed by immunodensitometry and ELISA, respectively.

Results

PDF exposure times from 15 min to 60 min resulted in progressively increased HSP-72 expression levels (267 vs 320 vs 419% of controls, p<0.05 vs controls) as well as increased IL-8 secretion (323 vs 528 vs 549% of controls, p<0.05 vs controls) with full cell viability (MTT unchanged to control). HSP-72 expression was statistically significantly correlated with IL-8 secretion. Conclusions: The significant correlation between HSP-72 expression and IL-8 secretion suggests that the regulation of pro-inflammatory pathways in mesothelial cells exposed to PDF may represent an integral part of their stress response. Future studies to investigate the cellular regulatory mechanism involved are warranted.
ECG-Triggered Muscular Counterpulsation for Treatment of Low Cardiac Output
Authors: Walpoth B.H. , Aregger C. , Lapanashvili L. , Mettler D. , Carrel T. , Hess O.M.
Published: January 2018

Background.

Skeletal muscular counterpulsation (MCP) has been used as a new non-invasive technique for treatment of low cardiac output. The MCP method is based on ECG-triggered skeletal muscle stimulation. The purpose of the present study was to evaluate acute hemodynamic changes induced by MCP in the experimental animal.

Methods.

Eight anaesthetized pigs (43±4 kg) were studied at rest and after IV β-blockade (10 mg propranolol) before and after MCP Muscular counterpulsation was performed on both thighs using trains (75 ms duration) of multiple biphasic electrical impulses with a width of 1 ms and a frequency of 200 Hz at low (10 V) and high (30 V) amplitude. ECG-triggering was used to synchronize stimulation to a given time point. LV pressure-volume relations were determined using the conductance catheter. After baseline measurements, MCP was carried out for 10 minutes at low and high stimulation amplitude. The optimal time point for MCP was determined from LV pressure-volume loops using different stimulation time points during systole and diastole. Best results were observed during end-systole and, therefore, this time point was used for stimulation.

Results.

Under control conditions, MCP was associated with a significant decrease in pulmonary vascular resistance (-18%), a decrease in systemic vascular resistance (-11%) and stroke work index (-4%), whereas cardiac index (+2%) and ejection fraction (+6%) increased slightly. Pressure-volume loops showed a leftward shift with a decrease in end-systolic volume. After β-blockade, cardiac function decreased (HR, MAP, EF, dP/dt max), but it improved with skeletal muscle stimulation (HR +10% and CI +17%, EF +5%). There was a significant decrease in pulmonary (-19%) and systemic vascular resistance (-29%).

Conclusions.

In the animal model, ECG-triggered skeletal muscular counterpulsation is associated with a significant improvement in cardiac function at baseline and after IV β-blockade. Thus, MCP represents a new, non-invasive technique which improves cardiac function by diastolic compression of the peripheral arteries and veins, with a decrease in systemic vascular resistance and increase in cardiac output.
Hepatitis C Virus Infection and Rituximab Therapy after Renal Transplantation
Authors: Fabrizi F. , Martin P. , Elli A. , Montagnino G. , Banfi G. , Passerini P. , Campise M.R. , Tarantino A. , Ponticelli C.
Published: January 2018

Background.

Rituximab, a chimeric monoclonal antibody, has been successfully given in various diseases including HCV-associated mixed cryoglobulinemia. However, only preliminary data exists on its efficacy and safety after renal transplantation.

Methods.

We report on a renal transplant recipient with chronic hepatitis C who received rituximab therapy for gastric cancer. Four rituximab infusions of 375 mg/m2 were given.

Results.

Rituximab therapy was complicated by cholestatic hepatitis C with very high HCV RNA levels; liver insufficiency occurred. The patient developed bacterial pneumoniae and respiratory insufficiency was the cause of death. Although other mechanisms cannot be excluded, we found that rituximab therapy was implicated in the pathogenesis of cholestatic hepatitis C in our patient.

Conclusions.

We suggest that rituximab therapy may be associated with significant side effects. More experience has to be accumulated before any conclusions on efficacy and safety of rituximab therapy after RT can be drawn.
State of the Art on Autologous Mesothelial Transplant in Animals and Humans
Authors: Di Paolo N. , Sacchi G. , Del Vecchio M.T. , Nicolai G. , Brardi S. , Garosi G.
Published: January 2018

Sixteen years ago rabbit and human mesothelial cells were successsfully cultured and autoimplanted. The aim of the study was merely to demostrate that mesothelial implant was possible and interesting not only in peritoneal dialysis, but also in the vaster field of medicine and surgery concerning all the mesothelial districts of the body.

The aim of this paper is to recollect the steps which have led to autolougous mesothelial transplantation and verify if the tecnique has been validated and adopted by others.

Review of the literature published in the last 15 years shows that intraperitoneal transplantation of mesothelial cells has been effective in reducing the formation of peritoneal adhesions, and in remodeling the area of mesothelial denudation. New studies on the mesothelial cell opened the way to costruction of transplantable tissue-engineered artificial peritoneum, to the utilization of mesothelial progenitor cells and to find simple metods to collect autologous mesothelial cells.

Finally mesothelial trasnsplantation may represent a new neovascular therapy in the prevention and treatment of ischemic coronaric heart disease.
The Origin of Regenerating Mesothelium: A Historical Perspective
Authors: Mutsaers S.E. , Prêle C. , Lansley S.M. , Herrick S.E.
Published: January 2018

Bichat first described the mesothelium in 1827 but despite its early discovery, it has only been in recent years that its importance both in health and disease has been realised. One area still poorly understood is that of the mechanisms regulating mesothelial repair. Mesothelial cells are derived from the mesoderm but express many epithelial characteristics. However, mesothelium does not heal in the same way as other epithelial-like cells. Epithelium heals by centripetal migration, with cells at the edge of the wound proliferating and migrating into the injured area. Hertzler in 1919 noted that both large and small peritoneal injuries healed within the same time frame, concluding that the mesothelium could not heal solely by centripetal migration. The exact mechanisms involved in mesothelial regeneration following injury are controversial with a number of proposals suggested to explain the origin of the regenerating cells. This review will examine these proposals and give some insights into the likely mechanisms involved.
Mesothelial Cells from Tunica Vaginalis, a Practical Source for Mesothelial Transplantation
Authors: Asano T. , Takazawa R. , Yamato M. , Kihara K. , Okano T.
Published: January 2018

Transplantation of mesothelial cells is used to repair peritoneum that is damaged by surgery, peritonitis, and peritoneal dialysis. The largest obstacle for clinical application of mesothelial cell transplantation is the lack of a reliable source of mesothelial cells. So far, they are isolated from omentum, mesentery, parietal wall and ascites. Procedures used to obtain mesothelial cells from the omentum or mesentery are invasive, however, especially in pre-operative situations. Sufficient amounts of ascites for aspiration can not be obtained under physiological conditions. We have developed a novel method of isolating mesothelial cells from the tunica vaginalis. The tunica vaginalis originates from the peritoneum and descends into the scrotum along with the testis during fetal development. This region provides a source of mesothelial cells that is convenient to approach and free from abdominal complications. Transplantation of autologous mesothelial cells that were isolated from tunica vaginalis was effective in preventing post-operative adhesions. In this review, we summarize mesothelial cell transplantation trials and describe the method of isolating mesothelial cells form the tunica vaginalis. Mesothelial cell transplantation might be widely accepted for clinical use in the near future.
PIV Validation of Blood-heart Valve Leaflet Interaction Modelling
Authors: Kaminsky R. , Dumont K. , Weber H. , Schroll M. , Verdonck P.
Published: January 2018

The aim of this study was to validate the 2D computational fluid dynamics (CFD) results of a moving heart valve based on a fluid-structure interaction (FSI) algorithm with experimental measurements. Firstly, a pulsatile laminar flow through a monoleaflet valve model with a stiff leaflet was visualized by means of Particle Image Velocimetry (PIV). The inflow data sets were applied to a CFD simulation including blood-leaflet interaction.

The measurement section with a fixed leaflet was enclosed into a standard mock loop in series with a Harvard Apparatus Pulsatile Blood Pump, a compliance chamber and a reservoir. Standard 2D PIV measurements were made at a frequency of 60 bpm. Average velocity magnitude results of 36 phase-locked measurements were evaluated at every 10° of the pump cycle. For the CFD flow simulation, a commercially available package from Fluent Inc. was used in combination with in-house developed FSI code based on the Arbitrary Lagrangian-Eulerian (ALE) method. Then the CFD code was applied to the leaflet to quantify the shear stress on it.

Generally, the CFD results are in agreement with the PIV evaluated data in major flow regions, thereby validating the FSI simulation of a monoleaflet valve with a flexible leaflet. The applicability of the new CFD code for quantifying the shear stress on a flexible leaflet is thus demonstrated. (Int J Artif Organs 2007; 30: 640–8)
Microbiology of Infection in Mechanical Circulatory Support
Authors: Holman W. L.
Published: January 2018

The results of MCSS therapy for patients with severe heart failure are improving, and there are increasing numbers of implants as device therapy enters the era of permanent use (i.e., destination therapy). Device-related infection of implanted pumps and sepsis remain important risk factors for death, and once infections are established on biomaterial surfaces they usually persist despite prolonged antimicrobial therapy.

This paper covers the topic of infection in mechanical circulatory support. Methods to prevent and manage infection are described. Recent information from the field of microbiology that is relevant to understanding device-related infection is reviewed, including the mechanisms for microbial adhesion to prosthetic surfaces, quorum sensing, and biofilm formation. Characteristics that are important to antimicrobial resistance of microbes dwelling in biofilms are described (e.g. responses to microenvironmental conditions that result in resistance to antibiotics). This information may lead to new therapies that further diminish rates of device infection, and allow complete eradication of infections when they occur.
Small-colony Variants (SCVs) of Staphylococci: A Role in Foreign Body-associated Infections
Authors: Von Eiff C. , Becker K.
Published: January 2018

Staphylococci have various strategies for resisting therapy that extend beyond classic mechanisms. Clinical experience with device-associated infections as well as with infections due to small-colony variants (SCVs) clearly shows that both antibacterial chemotherapy and host defense mechanisms are often unable to eliminate the pathogens and cure these infections. Of particular interest is the fact that in the past few years an increasing number of various foreign body-related infections due to staphylococcal SCVs have been reported. In this overview, the characteristics of SCVs recovered from clinical specimens and of defined mutants displaying the SCV phenotype are described. Their slow growth and changing biochemical and physiological features represent a challenge to clinical laboratory personnel, because recovery, identification, as well as susceptibility testing of these variants need particular efforts. In addition, the reduced susceptibility to aminoglycosides and the ability of SCVs to persist intracellularly require specific attention for the treatment of these infections. Thus, special efforts to search for these variants formed by Staphylococcus aureus or by coagulase-negative staphylococci should be considered when an infection is particularly resistant to therapy, persists for a long period or fails to respond to apparently adequate therapy with antimicrobial compounds.