Biomechanical validation of additively manufactured artificial femoral bones.

Replicating the mechanical behavior of human bones, especially cancellous bone tissue, is challenging. Typically, conventional bone models primarily consist of polyurethane foam surrounded by a solid shell. Although nearly isotropic foam components have mechanical properties similar to cancellous bone, they do not represent the anisotropy and inhomogeneity of bone architecture. To consider the architecture of bone, models were developed whose core was additively manufactured based on CT data. This core was subsequently coated with glass fiber composite. Specimens consisting of a gyroid-structure were fabricated using fused filament fabrication (FFF) techniques from different materials and various filler levels. Subsequent compression tests showed good accordance between the mechanical behavior of the printed specimens and human bone. The unidirectional fiberglass composite showed higher strength and stiffness than human cortical bone in 3-point bending tests, with comparable material behaviors being observed. During biomechanical investigation of the entire assembly, femoral prosthetic stems were inserted into both artificial and human bones under controlled conditions, while recording occurring forces and strains. All of the artificial prototypes, made of different materials, showed analogous behavior to human bone. In conclusion, it was shown that low-cost FFF technique can be used to generate valid bone models and selectively modify their properties by changing the infill.

Automatic two-channel sleep staging using a predictor-corrector method.

OBJECTIVE: We developed and implemented two predictor-corrector methods for the classification of two-channel EEG data into sleep stages. APPROACH: The sequence of sleep stages over the night is modeled by a Markov chain of first and second order, resulting in an informative prior distribution for the new state, given the distribution of the current one. The correction step is realized by applying a Bayes classifier using the (preprocessed) data and this prior. The preprocessing step consists of a frequency analysis, a log transformation and a dimensionality reduction via principal component analysis. MAIN RESULTS: The software automatically generates sleep profiles in which it detects wakeful phases as well as the different sleep stages with error rates of 16.5%-31.9% (n = 8, healthy subjects, mean age ± SD: 39 ± 8.1 years, five females), where we compared our results to those of a certified polysomnographic technologist, who used a full polysomnograph and rated according to the American Academy of Sleep Medicine (AASM) criteria. SIGNIFICANCE: The method presented relies on considerably less information than visual scoring and is done automatically. Furthermore, the error is comparable to visual scoring, where the inter-rater variability lies around 82%. Therefore, it has the potential to lessen the overheads associated with sleep diagnostics.

First Experiences with Navigated Radio-Guided Surgery Using Freehand SPECT.

BACKGROUND: Sentinel lymph node biopsy (SLNB) in melanoma using one-dimensional gamma probes is a standard of care worldwide. Reports on the performance are claimed by most groups to successfully detect the SLNs during the surgical procedure in almost 100% of the patients. In clinical practice, however, several issues remain which are usually not addressed: the difficulty of intraoperative detection of deeply located nodes, SLN detection in obese patients or in the groin and the impossibility to make a scan of the entire wound after SLN resection to avoid false negative testing for eventually remaining SLNs. MATERIALS AND METHODS: The concept behind freehand SPECT is to combine a gamma probe as used for conventional radio-guided surgery with a tracking system as used in neurosurgical navigation. From this combination and a proper algorithm framework the 3D reconstruction of radioactivity distributions and displaying these intraoperatively is possible. CONCLUSION: In summary, the feasibility of freehand SPECT could be shown and provides an image-guided SLNB and a truly minimally invasive and optimized surgical procedure.

Efficacy and safety of DALI LDL-apheresis at high blood flow rates: a prospective multicenter study.

Direct adsorption of lipids (DALI) is the first LDL-apheresis method compatible with whole blood. Usually, the blood flow rate is adjusted at 60-80 ml/min, which results in session times of about 2 hr. The present study was performed to test the safety and efficacy of low-density lipoprotein cholesterol (LDL-C) and lipoprotein (a) [Lp(a)] removal by DALI at high blood flow rates in order to reduce treatment time. Thirteen chronic DALI patients in seven centers suffering from hypercholesterolemia (LDL-C 162 +/- 42 mg/dl at baseline) and coronary artery disease were treated on a weekly or biweekly basis by DALI apheresis. The blood flow rate QB was held constant for at least two sessions, respectively, and was increased from 60 to 80, 120, 160, 200, and 240 ml/min. All patients had pre-existing av-fistulas. The anticoagulation was performed by a heparin bolus plus ACD-A at a ratio of citrate:blood ranging from 1:20 to 1:90. Clinically, the sessions were well tolerated and only 26/201 sessions (12%) of the treatments were fraught with minor adverse events. Acute LDL-C reductions (derived from LDL-C levels determined by lipoprotein electrophoresis) averaged 72/66/60/53/50/48% for QB=60/80/120/160/200/240 ml/min. Lp(a) reductions were 68/67/62/60/58/56%, whereas HDL-C losses were < or =10%. Routine blood chemistries and blood cell counts remained in the normal range. Treatment times averaged 142/83/45 min at Qb=60/120/240 ml/min. On average, DALI LDL-apheresis could be performed safely and effectively at high blood flow rates up to at least 120 ml/min in patients with good blood access, which significantly reduced treatment time from 142 to 83 min (-42%).

Ex vivo biocompatibility of a new beta2-microglobulin hemoperfusion polymer.

Beta2-microglobulin (beta2-m) is an 11.8 kD protein that is excreted by the kidneys. In renal insufficiency, it accumulates in the body and can result in AB amyloidosis with bone and joint destruction. Four modifications of a new beta2-m adsorbent material were tested for biocompatibility with human whole blood. 500 ml of heparinized blood from healthy human donors was perfused ex vivo through minicolumns (adsorber beads: divinylbenzene with different biocompatible coatings) in the single-pass mode. Blood samples were taken from the antecubital vein before and at the column outlet during the 50 min test runs. Red and white cell counts remained virtually constant. No signs of hemolysis could be detected. Thrombogenicity of the columns was low as shown by the insignificant platelet loss, only slight platelet activation and moderate thrombin-antithrombin formation. There was no activation of leukocytes nor monocytes. Complement and bradykinin activation was minimal. Electrolyte concentrations and pH remained essentially constant. In conclusion, this new beta2-m adsorbent material exhibited favorable biocompatibility features in our ex vivo model and is thus a promising candidate for future clinical beta2-m hemoperfusion studies in patients.

Modified DALI LDL-apheresis using trisodium citrate anticoagulation plus bicarbonate or lactate-buffered hemofiltration substitution fluids as primers.

BACKGROUND: DALI (direct adsorption of lipids) is the first LDL-apheresis technique able to adsorb low-density lipoprotein (LDL) and lipoproteina) directly from whole blood. In the standard procedure, acid citrate dextrose (ACD-A) is used as anticoagulation and the adsorber is rinsed with a specially manufactured priming solution (PS). Using neutral trisodium citrate (TSC) instead of ACD-A might improve the acid-base homeostasis during DALI apheresis; moreover, applying wholesale hemofiltration solutions instead of the special PS might avoid the use of two separate solutions for both priming before and reinfusion after the treatment, thus simplifiying the procedure. AIM: The present study was performed to test the effect of neutral (TSC) anticoagulation and of two different commercially available hemofiltration (HF) priming solutions on the efficacy and biocompatibility of DALI apheresis. MATERIALS AND METHODS: Five hypercholesterolemic chronic DALI patients were treated prospectively, on a weekly or biweekly basis, 3 times each by standard DALI-apheresis (A). by DALI using 4% TSC and bicarbonate-buffered HF BIC35-210 priming (B). as well as by DALI using 4% TSC and lactate-buffered HF 23 priming (C). After the sessions, the extracorporeal circuit (ECC) was rinsed with saline in study arm A and with the corresponding HF solutions in study arms B and C, respectively. RESULTS: Acute LDL-cholesterol reductions in the study arms A/B/C averaged 64/64/63%, for Lp(a) 62/64/62%, respectively (n=15). Clinically, all sessions were essentially uneventful and no clots were observed in the ECC. No major differences were found between the 3 study arms with respect to biocompatibility (elastase, C3a, thrombin-antithrombin, beta-thromboglobulin, bradykinin). CONCLUSION: DALI apheresis using TSC anticoagulation and HF solutions for both priming and reinfusion proved to be as safe and effective as the standard DALI apheresis. These modifications, however, further simplify the procedure.

Extracorporeal plasma treatment in primary and recurrent focal segmental glomerular sclerosis: a review.

This review summarizes the state of the art of apheresis in focal segmental sclerosing glomerulonephritis (FSGS) based on the current literature. FSGS is a major cause of nephrotic syndrome and renal insufficiency and has a high tendency to recur after renal transplantation. In many instances, treatment with steroids and/or immunosuppressive agents is without effect. Therapeutic plasma exchange (as well as immunoadsorption in some instances) was performed in primary (pFSGS) and recurrent (rFSGS) FSGS. Proteinuria could be improved and renal function was stabilized in 58% of rFSGS adults, in 74% of rFSGS children, and in 44% of pFSGS in adults. Treatment was successful if implemented early, i.e., in the stage of minimal change glomerulopathy before significant sclerosis had developed. This approach will probably be realistic only in the regular follow-up after transplantation. Furthermore, some patients with full-blown pFSGS were treated successfully in a prophylactic indication immediately prior to transplantation which decreased the incidence of recurrence to 26% in treated patients versus 54% in controls. Due to the uncontrolled study design and small patient cohorts in most trials, the major disadvantage of the reports currently available on the use of apheresis in FSGS is their low level of evidence from which the previous conclusions had to be drawn. Large prospective, controlled and randomized clinical trials are urgently needed for recommendations based on high-level evidence.

Extracorporeal plasma treatment in thrombotic thrombocytopenic purpura and hemolytic uremic syndrome: a review.

This review summarizes the state of the art of apheresis in hemolytic uremic syndrome (HUS) and in thrombotic thrombocytopenic purpura (TTP). Both entities are characterized by thrombotic microangiopathy, hemolytic anemia, and thrombocytopenia. While HUS often presents with renal insufficiency, cerebral involvement is more common in TTP. Recently, in TTP, a primary or secondary lack of activity of a von Willebrand factor (vWF) degrading enzyme was made responsible for the presence of unusually large vWF multimers causing platelet aggregation and thrombus formation in the microvasculature. In contrast, in familial HUS, a factor H deficiency with uninhibited complement activation seems to play a role. Therapeutic plasma exchange (TPE) using fresh frozen plasma or cryosupernatant as the substitution fluid is indicated in acute TTP and atypical HUS without antecedent diarrhea. As a rule, it will show good effectiveness, especially in the former entity. HUS in pregnancy should be treated by instant delivery whereas postpartum HUS may resolve using protracted courses of TPE. In contrast, in thrombotic microangiopathy after bone marrow transplantation as well as in HUS due to cancer, mitomycin C, or after renal transplantation, TPE is of questionable value and indicated only as a last resort treatment.

Improvement of hemorheology by DALI apheresis: acute effects on plasma viscosity and erythrocyte aggregation in hypercholesterolemic patients.

Plasma viscosity (PV) and erythrocyte aggregation (EA) are determinants of microcirculation, especially under the compromised hemodynamic conditions resulting from atherosclerosis. Direct adsorption of lipoproteins (DALI) apheresis is the first method for direct adsorption of lipoproteins; it drastically reduces low-density lipoprotein (LDL)-cholesterol and lipoprotein (a) (Lp[a]), and may therefore improve PV and EA. The current study was performed to test the effect of DALI on hemorheology. Six hypercholesterolemic patients who had been on regular LDL apheresis for at least several months were treated on a weekly or biweekly basis, on average 5 times each by DALI. Before and after each session, PV was measured by a capillary tube plasma viscosimeter and EA by rotational aggregometry. Single DALI sessions (n = 31) acutely decreased PV from 1.18 +/- 0.04 to 1.06 +/- 0.3 mPa (-10%) while EA improved from 22.8 +/- 4.4 to 13.3 +/- 4.5 (arbitrary units) (-42%). LDL-cholesterol, Lp(a), and very-low-density lipoprotein (VLDL)-cholesterol were effectively reduced while the decrease of triglycerides and fibrinogen was only moderate. DALI apheresis exerted an acute positive effect on blood hemorheology which may have beneficial effects on microcirculation. This hypothesis is in accordance with the clinical observation that in some patients, improvement of angina and/or exercise tolerance can be observed after only a few DALI sessions where changes of coronary stenoses cannot be expected yet.

Effect of low-dose citrate anticoagulation on the clinical safety and efficacy of direct adsorption of lipoproteins (DALI apheresis) in hypercholesterolemic patients: a prospective controlled clinical trial.

Direct adsorption of lipoproteins (DALI) is the first lipid apheresis system compatible with whole blood with the advantage of a very simple procedure. A mixture of heparin plus citrate (ACD-A) is used for the anticoagulation regimen (AR). A clinical, prospective, controlled crossover study was performed to test the safety and efficacy of low-dose citrate (LDC) anticoagulation in DALI. Five chronic DALI patients suffering from coronary heart disease and hypercholesterolemia underwent 3 DALI sessions each using the LDC anticoagulation regimen (60 IU heparin/kg body weight as initial bolus; 1:40 ACD-A: blood as perfusion). This was compared to 3 sessions per patient with the standard AR (bolus of 20 IU heparin/kg, 1:20 ACD-A as perfusion). Patient blood volumes (1.6; average of 7,040 ml) were treated with 750 ml adsorber gel per session at a blood flow rate of 60 ml/min. Mean LDL and Lp(a) reductions exceeded 60% with both AR. No clinical side effects were observed. Both AR controlled the coagulation well as evidenced by a sufficient prolongation of the partial prothrombin time (PTT) and activated clotting time as well as low thrombin-antithrombin (TAT) formation. Biocompatibility parameters exhibited favorable results (low activation of complement and cells, and only slight formation of C3a, C5a, beta-thromboglobulin, elastase, and TNF-alpha). The asymptomatic bradykinin generation was comparable in both study arms. LDC optimized the ionized calcium levels and pH in the efferent blood postadsorber. LDC anticoagulation was safe and effective, and may further improve the tolerance of DALI apheresis in hypercholesterolemic patients.

Heparin-free DALI LDL-apheresis in hyperlipidemic patients: efficacy, safety and biocompatibility.

BACKGROUND AND AIM OF STUDY: In routine DALI apheresis--the first technique for direct adsorption of lipoproteins from whole blood--heparin plus citrate (ACD-A) is used as anticoagulation regimen. However, recently several publications have warned of heparin-induced thrombocytopenia as a rare but potentially life-threatening complication of heparin administration (HIT type 2). The aim of the present study was therefore to test the efficacy and biocompatibility of DALI using a heparin-free anticoagulation regimen consisting exclusively of citrate. METHODS: Four symptomatic hypercholesterolemic patients on regular DALI apheresis were switched to the heparin-free protocol for two sessions each. Two of the patients were on oral anticoagulation using phenprocoumon. In the weekly sessions, 1.3 patient blood volumes were processed at a blood flow rate of 60 ml/min using ACD-A at a ratio of 1:20 (v/v) during adsorber priming and the session. RESULTS: Clinically, all sessions were essentially uneventful. Uncorrected lipoprotein reductions amounted to 65% for LDL-C, 62% for Lp(a), 53% for VLDL-C, 24% for HDL-C, 17% for triglycerides and 19% for fibrinogen. Cell counts remained virtually constant. No signs of hemolysis or clotting could be detected. Thromboplastin time (Quick) was slightly prolonged and partial thromboplastin time (PTT) moderately elevated in all patients. In contrast, whole blood coagulation time acc. to Lee-White and activated clotting times were increased only in orally anticoagulated patients. Biocompatibility in terms of complement, leukocyte and thrombocyte activation was excellent. Bradykinin activation was moderate peaking at 3038 pg/ml in the efferent line. Systemic thrombin-antithrombin complex (TAT) reflected perfect anticoagulation in orally anticoagulated patients and adequate anticoagulation in the patients without phenprocoumon. CONCLUSION: In this pilot study, heparin-free DALI apheresis was safe and effective and may thus be performed in LDL-apheresis dependent patients who suffer from heparin intolerance.

Workflow management systems--a powerful means to integrate radiologic processes and application systems.

This presentation describes a research project investigating the suitability of model-based Workflow Management Systems (WfMS) to support radiological process. The following aspects are covered: process modeling, process enactment, and architecture of workflow-enabled application systems.

Cooperative image workstation based on explicit models of diagnostic information requirements.

A medical image workstation designed to act as a cooperative dialogue partner in diagnostic radiology has been conceived, and a prototype has been made. The system can automatically select relevant information (eg, from current and previous examinations) and generate a meaningful and appropriate image arrangement on the display screen. For a number of routinely performed tasks in radiology, the users' interaction may be as simple as switching from one patient to the next. This is shown to considerably simplify and speed up radiological image access and presentation, saving the user time and effort. The cooperative system response is based on explicit (formalized and computer-accessible) models of diagnostic information requirements. These models are context dependent and take into account that diagnostic information needs vary with radiological work procedures, workstation users, and patient cases. Initial models have been acquired from expert radiologists in two European hospitals and were integrated in a cooperative workstation prototype. For the representation of models, rule-based and object-oriented techniques were applied. The rule base was designed with a distinct modular structure, separating between rule sets for general, task-dependent, and user-dependent information requirements. The installed rule-based mechanism also offers a solution for the automatic prefetching of images to avoid transmission delays in the course of diagnostic work sessions. The first part of the report reviews the objectives for the design of cooperative workstation user interfaces and explains the benefits from the users' point of view. In the second part, the acquisition, structuring, formalization, and representation of context-dependent information requirement models is described. The rule-based model is explained using examples. A layered workstation architecture consisting of model, object, and real-time layers is presented. Difficulties in the implementation of cooperative workstations are discussed that point to future research topics and standardization efforts.