Can I trust my fake data - A comprehensive quality assessment framework for synthetic tabular data in healthcare.

BACKGROUND: Ensuring safe adoption of AI tools in healthcare hinges on access to sufficient data for training, testing and validation. Synthetic data has been suggested in response to privacy concerns and regulatory requirements and can be created by training a generator on real data to produce a dataset with similar statistical properties. Competing metrics with differing taxonomies for quality evaluation have been proposed, resulting in a complex landscape. Optimising quality entails balancing considerations that make the data fit for use, yet relevant dimensions are left out of existing frameworks. METHOD: We performed a comprehensive literature review on the use of quality evaluation metrics on synthetic data within the scope of synthetic tabular healthcare data using deep generative methods. Based on this and the collective team experiences, we developed a conceptual framework for quality assurance. The applicability was benchmarked against a practical case from the Dutch National Cancer Registry. CONCLUSION: We present a conceptual framework for quality assuranceof synthetic data for AI applications in healthcare that aligns diverging taxonomies, expands on common quality dimensions to include the dimensions of Fairness and Carbon footprint, and proposes stages necessary to support real-life applications. Building trust in synthetic data by increasing transparency and reducing the safety risk will accelerate the development and uptake of trustworthy AI tools for the benefit of patients. DISCUSSION: Despite the growing emphasis on algorithmic fairness and carbon footprint, these metrics were scarce in the literature review. The overwhelming focus was on statistical similarity using distance metrics while sequential logic detection was scarce. A consensus-backed framework that includes all relevant quality dimensions can provide assurance for safe and responsible real-life applications of synthetic data. As the choice of appropriate metrics are highly context dependent, further research is needed on validation studies to guide metric choices and support the development of technical standards.

Impact of haemoglobin A1c on wound infection in patients with diabetes with implanted synthetic graft.

OBJECTIVE: The aim of this study was to assess the relationship between haemoglobin A1c (HbA1c) values and operative wound infection. METHOD: During the period from 2013-2016, consecutive patients with type 2 diabetes were prospectively evaluated. Data were retrospectively analysed. All included patients were admitted for an elective surgical procedure, requiring the use of prosthetic graft in a groin wound. The patients were divided into two groups according to their preoperative HbA1c values. The main outcome was groin wound infection. The association between preoperative long-term glycoregulation and wound infection was evaluated, as well as the impact of postoperative glycaemic values, regardless of the level of HbA1c. RESULTS: Of the 93 participating patients, wound infection occurred in 20 (21.5%). Wound infection occurred in 28.2% of patients with uncontrolled diabetes (HbA1c >7%) and 16.7% of patients with controlled diabetes (HbA1c <7%); however, the difference did not reach statistical significance (p=0.181). In regression modelling, operative time (p=0.042) was a significant predictor of wound infection, while patients' age (p=0.056) was on the borderline of statistical significance. Females had a higher probability for wound infection (odds ratio (OR): 1.739; 95% confidence interval (CI):0.483-6.265), but there was no statistical significance (p=0.397). Patients with elevated levels of HbA1c had a higher chance of wound infection compared with patients with controlled diabetes (OR: 2.243; 95% CI: 0.749-6.716), nevertheless, this was not statistically significant (p=0.149). CONCLUSION: We found no statistically significant correlation between elevated values of preoperative HbA1c and postoperative groin wound infection.

How Real-World Data Can Facilitate the Development of Precision Medicine Treatment in Psychiatry.

Precision medicine has the ambition to improve treatment response and clinical outcomes through patient stratification and holds great potential for the treatment of mental disorders. However, several important factors are needed to transform current practice into a precision psychiatry framework. Most important are 1) the generation of accessible large real-world training and test data including genomic data integrated from multiple sources, 2) the development and validation of advanced analytical tools for stratification and prediction, and 3) the development of clinically useful management platforms for patient monitoring that can be integrated into health care systems in real-life settings. This narrative review summarizes strategies for obtaining the key elements-well-powered samples from large biobanks integrated with electronic health records and health registry data using novel artificial intelligence algorithms-to predict outcomes in severe mental disorders and translate these models into clinical management and treatment approaches. Key elements are massive mental health data and novel artificial intelligence algorithms. For the clinical translation of these strategies, we discuss a precision medicine platform for improved management of mental disorders. We use cases to illustrate how precision medicine interventions could be brought into psychiatry to improve the clinical outcomes of mental disorders.

Analysis of Lower Extremity Amputations from the SerbVasc Registry.

BACKGROUND: Peripheral arterial disease (PAD) and diabetes are the major causes of lower extremity amputations (LEAs) worldwide. Morbidity and mortality in patients with LEAs are high with an associated significant burden on the global health system. The aim of this article is to report the overall morbidity and mortality rates after major and minor LEAs from the Serbian Vascular Registry (SerbVasc), with an analysis of predictive factors that influenced adverse outcomes. MATERIALS AND METHODS: SerbVasc was created in 2019 as a part of the Vascunet collaboration that is aiming to include all vascular procedures from 21 hospitals in Serbia. Prevalence of diabetes among patients with LEAs, previous revascularization procedures, the degree and the type of foot infection and tissue loss, and overall morbidity and mortality rates were analyzed, with a special reference to mortality predictors. RESULTS: In the period from January 2020 to December 2022, data on 702 patients with LEAs were extracted from the SerbVasc registry, mean age of 69.06±10.63 years. Major LEAs were performed in 59%, while minor LEAs in 41% of patients. Diabetes was seen in 65.1% of the patients, with 44% of them being on insulin therapy. Before LEA, only 20.3% of patients had previous peripheral revascularization. Soft tissue infection, irreversible acute ischemia, and Fontaine III and IV grade ischemia were the most common causes of above-the-knee amputations while diabetic foot was the most common cause of transphalangeal and toe amputations. The infection rate was 3.7%, the re-amputation rate was 5.7%, and the overall mortality rate was 6.9%, with intrahospital mortality in patients with above-the-knee amputation of 11.1%. The most significant intrahospital mortality predictors were age >65 years (p<0.001), chronic kidney disease (CKD) (p<0.001), ischemic heart disease (IHD) (p=0.001), previous myocardial revascularization (p=0.017), emergency type of admission (p<0.001), not using aspirin (p=0.041), using previous anticoagulation therapy (p=0.003), and postoperative complications (p<0.001). CONCLUSIONS: The main predictors of increased mortality after LEAs from the SerbVasc registry are age >65 years, CKD, IHD, previous myocardial revascularization, emergency type of admission, not using aspirin, using previous anticoagulation therapy, and postoperative complications. Taking into account high mortality rates after LEAs and a small proportion of previous peripheral revascularization, the work should be done on early diagnosis and timely treatment of PAD hopefully leading to decreased number of LEAs and overall mortality. CLINICAL IMPACT: Mortality after lower limb amputation from the SerbVasc register is high. A small number of previously revascularized patients is of particular clinical importance, bearing in mind that the main reasons for above-the-knee amputations were irreversible ischemia, Fontaine III and Fontaine IV grade ischemia. Lack of diagnostics procedures and late recognition of patients with PAD, led to subsequent threating limb ischemia and increased amputation rates. The work should be done on early diagnosis and timely treatment of PAD in Serbia, hopefully leading to an increased number of PAD procedures, decreased number of LEAs, and lower overall mortality.

Carotid Restenosis Rate After Stenting for Primary Lesions Versus Restenosis After Endarterectomy With Creation of Risk Index.

PURPOSE: Carotid artery stenting (CAS) is an option for carotid restenosis (CR) treatment with favorable outcomes. However, CAS has also emerged as an alternative to carotid endarterectomy (CEA) for the management of patients with primary carotid stenosis. This study aimed to report CR rates after CAS was performed in patients with primary lesions versus restenosis after CEA, to identify predictors of CR, and to report both neurological and overall outcomes. MATERIALS AND METHODS: From January 2000 to September 2018, a total of 782 patients were divided into 2 groups: The CAS (prim) group consisted of 440 patients in whom CAS was performed for primary lesions, and the CAS (res) group consisted of 342 patients with CAS due to restenosis after CEA. Indications for CAS were symptomatic stenosis/restenosis >70% and asymptomatic stenosis/restenosis >85%. A color duplex scan (CDS) of carotid arteries was performed 6 months after CAS, after 1 year, and annually afterward. Follow-up ranged from 12 to 88 months, with a mean follow-up of 34.6±18.0 months. RESULTS: There were no differences in terms of CR rate between the patients in the CAS (prim) and CAS (res) groups (8.7% vs 7.2%, χ2=0.691, p=0.406). The overall CR rate was 7.9%, whereas significant CR (>70%) rate needing re-intervention was 5.6%, but there was no difference between patients in the CAS (prim) and CAS (res) groups (6.4% vs 4.7%, p=0.351). Six independent predictors for CR were smoking, associated previous myocardial infarction and angina pectoris, plaque morphology, spasm after CAS, the use of FilterWire or Spider Fx cerebral protection devices, and time after stenting. A carotid restenosis risk index (CRRI) was created based on these predictors and ranged from -7 (minimal risk) to +10 (maximum risk); patients with a score >-4 were at increased risk for CR. There were no differences in terms of neurological and overall morbidity and mortality between the 2 groups. CONCLUSIONS: There was no difference in CR rate after CAS between the patients with primary stenosis and restenosis after CEA. A CRRI score >-4 is a criterion for identifying high-risk patients for post-CAS CR that should be tested in future randomized trials.

Intelligent digital tools for screening of brain connectivity and dementia risk estimation in people affected by mild cognitive impairment: the AI-Mind clinical study protocol.

More than 10 million Europeans show signs of mild cognitive impairment (MCI), a transitional stage between normal brain aging and dementia stage memory disorder. The path MCI takes can be divergent; while some maintain stability or even revert to cognitive norms, alarmingly, up to half of the cases progress to dementia within 5 years. Current diagnostic practice lacks the necessary screening tools to identify those at risk of progression. The European patient experience often involves a long journey from the initial signs of MCI to the eventual diagnosis of dementia. The trajectory is far from ideal. Here, we introduce the AI-Mind project, a pioneering initiative with an innovative approach to early risk assessment through the implementation of advanced artificial intelligence (AI) on multimodal data. The cutting-edge AI-based tools developed in the project aim not only to accelerate the diagnostic process but also to deliver highly accurate predictions regarding an individual's risk of developing dementia when prevention and intervention may still be possible. AI-Mind is a European Research and Innovation Action (RIA H2020-SC1-BHC-06-2020, No. 964220) financed between 2021 and 2026. First, the AI-Mind Connector identifies dysfunctional brain networks based on high-density magneto- and electroencephalography (M/EEG) recordings. Second, the AI-Mind Predictor predicts dementia risk using data from the Connector, enriched with computerized cognitive tests, genetic and protein biomarkers, as well as sociodemographic and clinical variables. AI-Mind is integrated within a network of major European initiatives, including The Virtual Brain, The Virtual Epileptic Patient, and EBRAINS AISBL service for sensitive data, HealthDataCloud, where big patient data are generated for advancing digital and virtual twin technology development. AI-Mind's innovation lies not only in its early prediction of dementia risk, but it also enables a virtual laboratory scenario for hypothesis-driven personalized intervention research. This article introduces the background of the AI-Mind project and its clinical study protocol, setting the stage for future scientific contributions.

Severe pacemaker pocket infection during the COVID-19 pandemic, transvenous lead removal.

INTRODUCTION: The estimated infection rate after permanent endocardial lead implantation is between 1% and 2%. Pacemaker lead endocarditis is treated with total removal of the infected device and proper antibiotics. In this case report, we present a patient with delayed diagnosis and treatment due to the COVID-19 outbreak. CASE REPORT: An 88-year-old, pacemaker dependent woman with diagnosed pacemaker pocket infection was admitted to the University Cardiovascular institute. The patient had a prolonged follow-up time due to the COVID-19 outbreak. She missed her routine checkup and came to her local hospital when the generator had already protruded completely, to the point where she held it in her own hand. Transthoracic echocardiogram showed possible vegetations on the lead. Transesophageal echocardiography was not performed due to the COVID-19 pandemic. On the day after the admission the patient underwent transvenous removal of the pacemaker lead using a 9 French gauge rotational extraction sheathe (Cook Medical). The extracted lead was covered in a thin layer of vegetations. Further follow-ups showed good recovery with no complications. CONCLUSIONS: A case showing delayed treatment of pacemaker pocket infection, due to delayed follow-up time during the COVID-19 pandemic. This patient underwent successful transvenous removal of the infected pacemaker lead, along with adequate antibiotic therapy, which has proven to be the most effective method of treating cardiac device-related endocarditis.

Analysis of outcomes of single-unit cord blood transplantation with umbilical cord blood units processed with two different red blood cell sedimentation reagents.

BACKGROUND: Various processing methodologies are routinely used to reduce volume and red blood cell content of umbilical cord blood (UCB) units collected for hematopoietic stem cell transplantation. There is limited information regarding effects of UCB processing techniques on clinical outcomes. STUDY DESIGN AND METHODS: Retrospective data analysis compared laboratory and clinical outcomes following single-unit UCB transplantation performed between 1999 and 2015. All UCB units were from St. Louis Cord Blood Bank and all were manually processed with either Hetastarch processed cord blood units (HCB) (n = 661) or PrepaCyte processed cord blood units (PCB) (n = 84). Additional sensitivity analysis focused on units transplanted from 2010 to 2015 and included 105 HCB and 84 PCB. RESULTS: There were no significant differences in patient characteristics between the two groups. Pre-freeze total nucleated and CD34+ cell counts, cell doses/kg of recipient weight, and total colony-forming units (CFUs) were higher in PCB compared with HCB. Post-thaw, the PCB group had a significantly better total nucleated cell recovery, while there were no significant differences in cell viability, CFU recovery, or CD34+ cell recovery. Primary analysis demonstrated faster neutrophil and platelet engraftment for PCB but no differences in overall survival (OS), whereas sensitivity analysis found no effect of processing method on engraftment, but better OS in the HCB group compared with PCB group. CONCLUSION: The UCB processing method had no significant impact on engraftment. However, we cannot completely exclude the effect of processing method on OS. Additional studies may be warranted to investigate the potential impact of the PCB processing method on clinical outcomes.

User-Intended Doppler Measurement Type Prediction Combining CNNs With Smart Post-Processing.

Spectral Doppler measurements are an important part of the standard echocardiographic examination. These measurements give insight into myocardial motion and blood flow, providing clinicians with parameters for diagnostic decision making. Many of these measurements are performed automatically with high accuracy, increasing the efficiency of the diagnostic pipeline. However, full automation is not yet available because the user must manually select which measurement should be performed on each image. In this work, we develop a pipeline based on convolutional neural networks (CNNs) to automatically classify the measurement type from cardiac Doppler scans. We show how the multi-modal information in each spectral Doppler recording can be combined using a meta parameter post-processing mapping scheme and heatmaps to encode coordinate locations. Additionally, we experiment with several architectures to examine the tradeoff between accuracy, speed, and memory usage for resource-constrained environments. Finally, we propose a confidence metric using the values in the last fully connected layer of the network and show that our confidence metric can prevent many misclassifications. Our algorithm enables a fully automatic pipeline from acquisition to Doppler spectrum measurements. We achieve 96% accuracy on a test set drawn from separate clinical sites, indicating that the proposed method is suitable for clinical adoption.

Unlicensed Umbilical Cord Blood Units Provide a Safe and Effective Graft Source for a Diverse Population: A Study of 2456 Umbilical Cord Blood Recipients.

Umbilical cord blood (UCB) transplantation (UCBT) is a curative procedure for patients with hematologic malignancies and genetic disorders and expands access to transplantation for non-Caucasian patients unable to find a fully matched unrelated donor. In 2011, the US Food and Drug Administration required that unrelated UCBT be performed using either licensed UCB or unlicensed UCB under the Investigational New Drug (IND) program. The National Marrow Donor Program manages an IND under which 2456 patients (1499 adults and 957 children, 564 with malignant diseases and 393 with nonmalignant diseases) underwent single or double UCBT between October 2011 and December 2016. The median patient age was 31 years (range, <1 to 81 years), and 50% of children and 36% of adults were non-Caucasian. The median time to neutrophil engraftment (ie, absolute neutrophil count ≥500/mm3) was 22 days for adults, 20 days for pediatric patients with malignant diseases, and 19 days for pediatric patients with nonmalignant diseases, with corresponding rates of engraftment at 42 days of 89%, 88%, and 90%. In these 3 groups of patients, the incidence of acute graft-versus-host disease (GVHD) grade II-IV was 35%, 32%, and 24%; the incidence of chronic GVHD was 24%, 26%, and 24%; and 1-year overall survival (OS) was 57%, 71%, and 79%, respectively. In multivariate analysis, younger age, lower Hematopoietic Cell Transplantation-Specific Comorbidity Index, early-stage chemotherapy-sensitive disease, and higher performance score were predictive of improved OS for adults. In a subset analysis of children with malignancies undergoing single UCBT, the use of either licensed UCB (n = 48) or unlicensed UCB (n = 382) was associated with similar engraftment and survival. The use of unlicensed UCB units is safe and effective and provides an important graft source for a diverse population.

An image fusion tool for echo-guided left ventricular lead placement in cardiac resynchronization therapy: Performance and workflow integration analysis.

BACKGROUND: The response rate to cardiac resynchronization therapy (CRT) may be improved if echocardiographic-derived parameters are used to guide the left ventricular (LV) lead deployment. Tools to visually integrate deformation imaging and fluoroscopy to take advantage of the combined information are lacking. METHODS: An image fusion tool for echo-guided LV lead placement in CRT was developed. A personalized average 3D cardiac model aided visualization of patient-specific LV function in fluoroscopy. A set of coronary venography-derived landmarks facilitated registration of the 3D model with fluoroscopy into a single multimodality image. The fusion was both performed and analyzed retrospectively in 30 cases. Baseline time-to-peak values from echocardiography speckle-tracking radial strain traces were color-coded onto the fused LV. LV segments with suspected scar tissue were excluded by cardiac magnetic resonance imaging. The postoperative augmented image was used to investigate: (a) registration accuracy and (b) agreement between LV pacing lead location, echo-defined target segments, and CRT response. RESULTS: Registration time (264 ± 25 seconds) and accuracy (4.3 ± 2.3 mm) were found clinically acceptable. A good agreement between pacing location and echo-suggested segments was found in 20 (out of 21) CRT responders. Perioperative integration of the proposed workflow was successfully tested in 2 patients. No additional radiation, compared with the existing workflow, was required. CONCLUSIONS: The fusion tool facilitates understanding of the spatial relationship between the coronary veins and the LV function and may help targeted LV lead delivery.

Outcomes of processing of bone marrow harvests for hematopoietic stem cell transplantation in pediatric patients utilizing a novel red blood cell sedimentation kit.

BACKGROUND: Bone marrow (BM) grafts are often subject to manipulation to minimize infusion volume, to deplete red blood cells (RBCs), to deplete plasma, and/or to achieve optimal concentration of nucleated cells (NCs) for freezing. Here, we report results of processing and infusion of four major ABO-incompatible BM grafts for allogeneic hematopoietic transplantation in pediatric patients. CASES AND METHODS: Patients ranging in age from 5 months to 18 years received hematopoietic stem cell transplantation for benign or malignant indications. Allogeneic BM grafts were processed using PrepaCyte-CB kits, approved by the Food and Drug Administration for enrichment of mononuclear cells in cord blood units for hematopoietic transplantation. Resulting grafts were dosed and infused using standard institutional protocol. After transplantation patients were evaluated for hematologic recovery. RESULTS: The PrepaCyte-CB processing method achieved on average 97.1% depletion of RBCs and 68.5% volume reduction, with a fairly efficient NC recovery (total NCs, 85.6%; white blood cells, 89.7%; CD34+ cells, 103.3%; and colony-forming unit cells, 87.5%). No microbial contamination was detectable in any of the processed grafts. Infusions were well tolerated, and all four patients achieved durable hematopoietic engraftment within expected time interval. CONCLUSION: Our results suggest that PrepaCyte-CB is safe and effective for minimal processing of BM grafts. Engraftment outcomes were comparable with other published BM processing methods. In addition, NC recovery achieved using this method appears to exceed that of previously described sedimentation reagents such as hetastarch and Ficoll.

Method comparison for cardiac image registration of coronary computed tomography angiography and 3-D echocardiography.

Treatment decision for coronary artery disease (CAD) is based on both morphological and functional information. Image fusion of coronary computed tomography angiography (CCTA) and three-dimensional echocardiography (3DE) could combine morphology and function into a single image to facilitate diagnosis. Three semiautomatic feature-based methods for CCTA/3DE registration were implemented and applied on CAD patients. Methods were verified and compared using landmarks manually identified by a cardiologist. All methods were found feasible for CCTA/3DE fusion.

Awareness of cord blood collection and the impact on banking.

BACKGROUND: Umbilical cord blood (UCB) is an important source of hematopoietic stem cells for transplantation especially in minority populations with limited chances of finding a histocompatible volunteer donor in the registry. UCB has the advantages of early availability, successful outcomes despite some histocompatibility mismatch, and low incidence of chronic graft-versus-host disease. Public cord blood banks that disseminate UCB products for transplant depend on voluntary donation at participating hospitals and obstetrical providers for collection. PROCEDURE: Using survey questionnaires, we evaluated attitudes toward UCB donation, the frequency of donation, and provider opinions on UCB collection in the greater St. Louis metropolitan area that caters to minority ethnicities in significant numbers. RESULTS: Our data suggest that nervousness and lack of information regarding the donation and utility of the product were ubiquitous reasons for not donating. Additionally, irrespective of age or level of education, women relied on healthcare providers for information regarding UCB donation. Providers reported primarily time constraints to discussing UCB donation at prenatal visits (54%). Of the interviewees, 62% donated UCB. Fallout due to refusal or preferring private banking was miniscule. CONCLUSIONS: These results suggest that dedicated personnel focused on disseminating information, obtaining consent, and collecting the UCB product at major hospitals can enrich cord blood banks especially with minority cords. Sustained and focused efforts could improve upon a relatively high wastage rate and ensure a robust supply of UCB products at local public banks.

Evaluation of Tissue Homogenization to Support the Generation of GMP-Compliant Mesenchymal Stromal Cells from the Umbilical Cord.

Recent studies have demonstrated that the umbilical cord (UC) is an excellent source of mesenchymal stromal cells (MSCs). However, current protocols for extracting and culturing UC-MSCs do not meet current good manufacturing practice (cGMP) standards, in part due to the use of xenogeneic reagents. To support the development of a cGMP-compliant method, we have examined an enzyme-free isolation method utilizing tissue homogenization (t-H) followed by culture in human platelet lysate (PL) supplemented media. The yield and viability of cells after t-H were comparable to those obtained after collagenase digestion (Col-D). Importantly, kinetic analysis of cultured cells showed logarithmic growth over 10 tested passages, although the rate of cell division was lower for t-H as compared to Col-D. This slower growth of t-H-derived cells was also reflected in their longer population doubling time. Interestingly, there was no difference in the expression of mesenchymal markers and trilineage differentiation potential of cells generated using either method. Finally, t-H-derived cells had greater clonogenic potential compared to Col-D/FBS but not Col-D/PL and were able to maintain CFU-F capacity through P7. This bench scale study demonstrates the possibility of generating therapeutic doses of good quality UC-MSCs within a reasonable length of time using t-H and PL.

Parametric ultrasound and fluoroscopy image fusion for guidance of left ventricle lead placement in cardiac resynchronization therapy.

Recent studies show that the response rate to cardiac resynchronization therapy (CRT) could be improved if the left ventricle (LV) is paced at the site of the latest mechanical activation, but away from the myocardial scar. A prototype system for CRT lead placement guidance that combines LV functional information from ultrasound with live x-ray fluoroscopy was developed. Two mean anatomical models, each containing LV epi-, LV endo- and right ventricle endocardial surfaces, were computed from a database of 33 heart failure patients as a substitute for a patient-specific model. The sphericity index was used to divide the observed population into two groups. The distance between the mean and the patient-specific models was determined using a signed distance field metric (reported in mm). The average error values for LV epicardium were [Formula: see text] and for LV endocardium were [Formula: see text]. The validity of using average LV models for a CRT procedure was tested by simulating coronary vein selection in a group of 15 CRT candidates. The probability of selecting the same coronary branch, when basing the selection on the average model compared to a patient-specific model, was estimated to be [Formula: see text]. This was found to be clinically acceptable.

Donor body mass index is an important factor that affects peripheral blood progenitor cell yield in healthy donors after mobilization with granulocyte-colony-stimulating factor.

BACKGROUND: The use of hematopoietic progenitor cell (HPC) transplantation has rapidly expanded in recent years. Currently, several sources of HPCs are available for transplantation including peripheral blood HPCs (PBPCs), cord blood cells, and marrow cells. Of these, PBPC collection has become the major source of HPCs. An important variable in PBPC collection is the response to PBPC mobilization, which varies significantly and sometime causes mobilization failure. STUDY DESIGN AND METHODS: A retrospective study of 69 healthy donors who underwent PBPC donation by leukapheresis was performed. All of these donors received 10 µg/kg/day or more granulocyte-colony-stimulating factor (G-CSF) for 5 days before PBPC harvest. Donor factors were evaluated and correlated with mobilization responses, as indicated by the precollection CD34 count (pre-CD34). RESULTS: Donors with a pre-CD34 of more than 100 × 10(6) /L had higher body mass index (BMI) compared with donors whose pre-CD34 was 38 × 10(6) to 99 × 10(6) /L or less than 38 × 10(6) /L (32.0 ± 1.04 kg/m(2) vs. 28.7 ± 0.93 kg/m(2) vs. 25.9 ± 1.27 kg/m(2) , respectively; p < 0.05). In addition, donors with high BMIs had higher pre-CD34 on a per-kilogram-of-body-weight basis compared with donors with low BMIs. CONCLUSION: BMI is an important factor that affects donor's response to mobilization and consequently the HPC yield. This effect may be due to a relatively high dose of G-CSF administered to donors with higher BMI or due to the presence of unknown intrinsic factors affecting mobilization that correlate with the amount of adipose tissue in each donor.

Culture of mouse amniotic fluid-derived cells on irradiated STO feeders results in the generation of primitive endoderm cell lines capable of self-renewal in vitro.

The cells present in amniotic fluid (AF) are currently used for prenatal diagnosis of fetal anomalies but are also a potential source of cells for cell therapy. To better characterize putative progenitor cell populations present in AF, we used culture conditions that support self-renewal to determine if these promoted the generation of stable cell lines from AF-derived cells (AFC). Cells isolated from E11.5 mouse were cultured on irradiated STO fibroblast feeder layers in human embryonic germ cell derivation conditions. The cultures grew multicellular epithelial colonies that could be repropagated from single cells. Reverse transcription semiquantitative polymerase chain reaction of established cell lines revealed that they belonged to the extraembryonic endoderm (ExEn) expressing high levels of Gata6, Gata4, Sox17, Foxa2 and Sox7 mRNA. Hierarchical clustering based on the whole transcriptome expression profile of the AFC lines (AFCL) shows significant correlation between transcription profiles of AFCL and blastocyst-derived XEN, an ExEn cell line. In vitro differentiation of AFCL results in the generation of cells expressing albumin and α-fetoprotein (AFP), while intramuscular injection of AFCL into immunodeficient mice produced AFP-positive tumors with primitive endodermal appearance. Hence, E11.5 mouse AF contains cells that efficiently produce XEN lines. These AF-derived XEN lines do not spontaneously differentiate into embryonic-type cells but are phenotypically stable and have the capacity for extensive expansion. The lack of requirement for reprogramming factors to turn AF-derived progenitor cells into stable cell lines capable of massive expansion together with the known ability of ExEn to contribute to embryonic tissue suggests that this cell type may be a candidate for banking for cell therapies.