Toward reproducible tumor organoid culture: focusing on primary liver cancer.

Organoids present substantial potential for pushing forward preclinical research and personalized medicine by accurately recapitulating tissue and tumor heterogeneity in vitro. However, the lack of standardized protocols for cancer organoid culture has hindered reproducibility. This paper comprehensively reviews the current challenges associated with cancer organoid culture and highlights recent multidisciplinary advancements in the field with a specific focus on standardizing liver cancer organoid culture. We discuss the non-standardized aspects, including tissue sources, processing techniques, medium formulations, and matrix materials, that contribute to technical variability. Furthermore, we emphasize the need to establish reproducible platforms that accurately preserve the genetic, proteomic, morphological, and pharmacotypic features of the parent tumor. At the end of each section, our focus shifts to organoid culture standardization in primary liver cancer. By addressing these challenges, we can enhance the reproducibility and clinical translation of cancer organoid systems, enabling their potential applications in precision medicine, drug screening, and preclinical research.

Variations in Electronic Health Record-Based Definitions of Diabetic Retinopathy Cohorts: A Literature Review and Quantitative Analysis.

Purpose: Use of the electronic health record (EHR) has motivated the need for data standardization. A gap in knowledge exists regarding variations in existing terminologies for defining diabetic retinopathy (DR) cohorts. This study aimed to review the literature and analyze variations regarding codified definitions of DR. Design: Literature review and quantitative analysis. Subjects: Published manuscripts. Methods: Four graders reviewed PubMed and Google Scholar for peer-reviewed studies. Studies were included if they used codified definitions of DR (e.g., billing codes). Data elements such as author names, publication year, purpose, data set type, and DR definitions were manually extracted. Each study was reviewed by ≥ 2 authors to validate inclusion eligibility. Quantitative analyses of the codified definitions were then performed to characterize the variation between DR cohort definitions. Main Outcome Measures: Number of studies included and numeric counts of billing codes used to define codified cohorts. Results: In total, 43 studies met the inclusion criteria. Half of the included studies used datasets based on structured EHR data (i.e., data registries, institutional EHR review), and half used claims data. All but 1 of the studies used billing codes such as the International Classification of Diseases 9th or 10th edition (ICD-9 or ICD-10), either alone or in addition to another terminology for defining disease. Of the 27 included studies that used ICD-9 and the 20 studies that used ICD-10 codes, the most common codes used pertained to the full spectrum of DR severity. Diabetic retinopathy complications (e.g., vitreous hemorrhage) were also used to define some DR cohorts. Conclusions: Substantial variations exist among codified definitions for DR cohorts within retrospective studies. Variable definitions may limit generalizability and reproducibility of retrospective studies. More work is needed to standardize disease cohorts. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Variable Selection When Estimating Effects in External Target Populations.

External validity is an important part of epidemiologic research. To validly estimate effects in specific external target populations using a chosen effect measure (i.e., "transport"), some methods require that one account for all effect measure modifiers [EMMs]. However, little is known about how including other variables that are not EMMs (i.e., non-EMMs) in adjustment sets impacts estimates. Using simulations, we evaluated how inclusion of non-EMMs affected estimation of the transported risk difference (RD) by assessing impacts of covariates that A) differ (or not) between the trial and the target, B) are associated with the outcome (or not), and C) modify the RD (or not). We assessed variation and bias when covariates with each possible combination of these factors were used to transport RDs using outcome modeling or inverse odds weighting. Including variables that differed in distribution between the populations but were non-EMMs reduced precision, regardless of whether they were associated with the outcome. However, non-EMMs associated with selection did not amplify bias resulting from omitting necessary EMMs. Including all variables associated with the outcome may result in unnecessarily imprecise estimates when estimating treatment effects in external target populations.

Variability in perfusion conditions and set-up parameters used in ex vivo human placenta models: A literature review.

The ex vivo human placenta perfusion model has proven to be clinically relevant to study transfer- and fetal exposure of various drugs. Although the method has existed for a long period, the setup of the perfusion model has not been generalized yet. This review aims to summarize the setups of ex vivo placental perfusion models used to examine drug transfer across the placenta to identify generalized properties and differences across setups. A literature search was carried out in PubMed September 26, 2022. Studies were labeled as relevant when information was reported, between 2000 and 2022, on the setups of ex vivo placental perfusion models used to study drug transfer across the placenta. The placenta perfusion process, and the data extraction, was divided into phases of preparation, control, drug, and experimental reflecting the chronological timeline of the different phases during the entire placental perfusion process. 135 studies describing an ex vivo human placental perfusion experiment were included. Among included studies, the majority (78.5%) analyzed drug perfusion in maternal to fetal direction, 18% evaluated bi-directional drug perfusion, 3% under equilibrium conditions, and one study investigated drug perfusion in fetal to maternal direction. This literature review facilitates the comparison of studies that employ similar placenta perfusion protocols for drug transfer studies and reveals significant disparities in the setup of these ex vivo placental perfusion models. Due to interlaboratory variability, perfusion studies are not readily comparable or interchangeable. Therefore, a stepwise protocol with multiple checkpoints for validating placental perfusion is needed.

The unique identifier as one of the essential tools for steering universal health coverage: The case of Morocco / L'identifiant unique comme un des instruments indispensables au pilotage de la couverture sanitaire universelle, le cas du Maroc.

INTRODUCTION: Morocco is carrying out several actions to generalize basic compulsory health insurance (CHI). Managing this project requires coordination, information sharing, and the commitment of all actors to the goal of covering an additional 22 million people. One of the key factors for achieving this objective is the implementation of a unified registration system. PURPOSE OF THE RESEARCH: The aim is to analyze the existing situation and the feasibility of implementing a unified registration system, and to describe the potential positive impact of the latter on the extension of CHI. RESULTS: This work is based on a diagnosis of the current situation. It draws on the legal framework, all available documents and figures, and on an analytical reading supported by existing literature. It reveals that due to the inadequacy or even the absence of an appropriate legal basis, each managing body has its own registration system. The lack of a unified system has given rise to a number of constraints. These concern, among other things: (i) mobility between or within schemes, which does not operate smoothly because it leads to re-registration (ii) inadequate monitoring of double benefit claims, which is the case for more than one scheme, due to insufficient and hesitant anti-fraud action (iii) the sharing and use of reliable data, which hinders decision making, evaluation, and monitoring. CONCLUSIONS: It is essential to adopt legal texts that will provide the basis for a unified system with regulations enabling the participation of all stakeholders, with the aim of steering the roll-out of CHI effectively and efficiently.

Introduction: Le Maroc mène, depuis quelques années, plusieurs actions permettant de généraliser l'assurance maladie obligatoire (AMO). Le pilotage de ce chantier nécessite la coordination, le partage d'informations et l'engagement de tous les acteurs afin de couvrir 22 millions de personnes supplémentaires. L'un des éléments clés pour optimiser la réalisation de cet objectif consiste à mettre en place un système unifié d'immatriculation. But de l'étude: Analyser l'existant et la faisabilité de la mise en place d'un système unifié d'immatriculation, tout en précisant ses retombées positives sur l'extension de l'AMO. Résultats: Ce travail, fondé sur un diagnostic, appuyé par l'arsenal juridique, des documents et des chiffres disponibles ainsi qu'une lecture analytique renforcée par la littérature existante, a permis de constater que, du fait de l'insuffisance voire l'absence d'un soubassement juridique adapté, chaque organisme gestionnaire a son propre système d'immatriculation. L'absence d'un système unifié gêne notamment : 1) la mobilité entre régimes ou intra-régimes, étant donné qu'elle ne se fait pas de manière fluide car elle génère la ré-immatriculation ; 2) le contrôle du double bénéfice d'un régime insuffisamment organisé et incapable de lutter contre la fraude ; 3) le partage et l'exploitation de données fiables empêchant d'assurer de manière appropriée le suivi, l'évaluation et la prise de décision. Conclusion: Il est indispensable d'adopter des textes juridiques pour fonder un système unifié qui permettra l'encadrement et l'engagement de toutes les parties prenantes dans l'objectif de piloter la généralisation de l'AMO avec efficacité et efficience.

Characterization of Secondary Metabolites of Leaf Buds from Some Species and Hybrids of Populus by Gas Chromatography Coupled with Mass Detection and Two-Dimensional High-Performance Thin-Layer Chromatography Methods with Assessment of Their Antioxidant Activity.

Poplars provide medicinal raw plant materials used in pharmacy. Leaf buds are one of the herbal medicinal products collected from poplars, having anti-inflammatory and antiseptic properties, but there are no quality standards for their production and there is a need to determine their botanical sources. Therefore, the chemical compositions of the leaf buds from four species and varieties of poplars, Populus balsamifera, P. × berolinensis, P. × canadensis 'Marilandica', and P. wilsonii were investigated and compared using gas chromatography coupled with mass detection (GC-MS) and two-dimensional high-performance thin-layer chromatography (2D-HPTLC) in order to search for taxa characterized by a high content of biologically active compounds and with a diverse chemical composition that determines their therapeutic effects. The presence of 163 compounds belonging to the groups of flavonoids, phenolic acids derivatives, glycerides, and sesquiterpenes was revealed. Moreover, the conditions for the separation and identification of biologically active compounds occurring in analyzed leaf buds using 2D-HPTLC were optimized and used for metabolomic profiling of the studied poplars, enabling their fast and simple botanical identification. The total phenolic (TPC) and flavonoid (TFC) contents of examined extracts were determined and their antioxidant capacities were estimated by spectrophotometric DPPH, ABTS, and FRAP assays. Based on the analysis of phytochemicals and antioxidant activity, P. × berolinensis buds were selected as the raw plant material for medicinal purposes with the highest content of active compounds and the strongest antioxidant activity.

FoodEx2 Harmonization of the Food Consumption Database from the Italian IV SCAI Children's Survey.

Estimating the habitual food and nutrient intakes of a population is based on dietary assessment methods that collect detailed information on food consumption. Establishing the list of foods to be used for collecting data in dietary surveys is central to standardizing data collection. Comparing foods across different data sources is always challenging. Nomenclatures, detail, and classification into broad food groups and sub-groups can vary considerably. The use of a common system for classifying and describing foods is an important prerequisite for analyzing data from different sources. At the European level, EFSA has addressed this need through the development and maintenance of the FoodEx2 classification system. The aim of this work is to present the FoodEx2 harmonization of foods, beverages, and food supplements consumed in the IV SCAI children's survey carried out in Italy. Classifying foods into representative food categories predefined at European level for intake and exposure assessment may lead to a loss of information. On the other hand, a major advantage is the comparability of data from different national databases. The FoodEx2 classification of the national food consumption database represented a step forward in the standardization of the data collection and registration. The large use of FoodEx2 categories at a high level of detail (core and extended terms) combined with the use of descriptors (facets) has minimized information loss and made the reference food categories at country level comparable with different food databases at national and international level.

Development of a validated assessment tool for medical students using simulated patients: an 8-year panel survey.

BACKGROUND: The use of simulated patients (SPs) to assess medical students' clinical performance is gaining prominence, underscored by patient safety perspective. However, few reports have investigated the validity of such assessment. Here, we examined the validity and reliability of an assessment tool that serves as a standardized tool for SPs to assess medical students' medical interview. METHODS: This longitudinal survey was conducted at Keio University School of Medicine in Japan from 2014 to 2021. To establish content validity, the simulated patient assessment tool (SPAT) was developed by several medical education specialists from 2008 to 2013. A cohort of 36 SPs assessed the performance of 831 medical students in clinical practice medical interview sessions from April 2014 to December 2021. The assessment's internal structure was analyzed using descriptive statistics (maximum, minimum, median, mean, and standard deviation) for the SPAT's 13 item total scores. Structural validity was examined with exploratory factor analysis, and internal consistency with Cronbach's alpha coefficients. The mean SPAT total scores across different SPs and scenarios were compared using one way analysis of variance (ANOVA). Convergent validity was determined by correlating SPAT with the post-clinical clerkship obstructive structured clinical examination (post-CC OSCE) total scores using Pearson's correlation coefficient. RESULTS: Of the 831 assessment sheets, 36 with missing values were excluded, leaving 795 for analysis. Thirty-five SPs, excluding one SP who quit in 2014, completed 795 assessments, for a response rate of 95.6%. Exploratory factor analysis revealed two factors, communication and physician performance. The overall Cronbach's alpha coefficient was 0.929. Significant differences in SPAT total scores were observed across SPs and scenarios via one-way ANOVA. A moderate correlation (r =.212, p <.05) was found between SPAT and post-CC OSCE total scores, indicating convergent validity. CONCLUSIONS: Evidence for the validity of SPAT was examined. These findings may be useful in the standardization of SP assessment of the scenario-based clinical performance of medical students.

Tailoring Transfection for Cardiomyocyte Cell Lines: Balancing Efficiency and Toxicity in Lipid versus Polymer-Based Transfection Methods in H9c2 and HL-1 Cells.

Cardiovascular research relies heavily on the veracity of in vitro cardiomyocyte models, with HL-1 and H9c2 cell lines at the forefront due to their cardiomyocyte-like properties. However, the variability stemming from non-standardized culturing and transfection methods poses a significant challenge to data uniformity and reliability. In this study, we introduce meticulously crafted protocols to enhance the culture and transfection of HL-1 and H9c2 cells, emphasizing the reduction of cytotoxic effects while improving transfection efficiency. Through the examination of polymer-based and lipid-based transfection methods, we offer a comparative analysis that underscores the heightened efficiency and reduced toxicity of these approaches. Our research provides an extensive array of step-by-step procedures designed to foster robust cell cultures and outlines troubleshooting practices to rectify issues of low transfection rates. We discuss the merits and drawbacks of both transfection techniques, equipping researchers with the knowledge to choose the most fitting method for their experimental goals. By offering a definitive guide to these cell lines' culturing and transfection, our work seeks to set a new standard in procedural consistency, ensuring that the cardiovascular research community can achieve more dependable and reproducible results, thereby pushing the boundaries of current methodologies toward impactful clinical applications.

Shear-Wave Elastography of the Achilles tendon: reliability analysis and impact of parameters modulating elasticity values.

PURPOSE: Shear wave elastography (SWE) has seen many advancements in Achilles tendon evaluation in recent years, yet standardization of this technique is still problematic due to the lack of knowledge regarding the optimal way to perform the examination. The purpose of this study was to evaluate the effects of ankle position, probe frequency and physical effort on the shear modulus of the Achilles tendon, but also to determine the intra and inter-observer reliability of the technique. METHODS: 37 healthy volunteers were included; SWE protocol was performed by two examiners. We analyzed the shear modulus of the tendon with the ankle in neutral, maximum dorsiflexion and maximum plantar flexion using two different high frequency probes. Afterwards, the subjects performed a brief physical exercise and SWE measurements were repeated. RESULTS: The L18-5 probe showed the highest ICC values (ICC = 0.798, 95% CI 0.660-0.880, p < 0.001) when positioned at 2 cm from the calcaneal insertion with the ankle in a neutral state. Conversely, utilizing the same L18-5 probe at 1 cm from the insertion during maximum plantar flexion of the ankle resulted in the lowest ICC (ICC = 0.422, 95% CI 0.032-0.655, p = 0.019). Significant variations in elasticity values were noted among different ankle positions and probe types, while no significant changes in elasticity were observed post-physical exercise. CONCLUSION: Ankle position and probe frequency are factors that influence elasticity values of the Achilles tendon. An ankle position between 10 and 20 degrees of plantar flexion is the most suitable for SWE evaluation. However, more research focusing on Achilles tendon SWE is essential due to the challenges encountered in standardizing this region.

Agreement between routinely used immunoassays for thyroid function testing in non-pregnant and pregnant adults.

OBJECTIVE: Thyroid function tests are common biochemical analyses, and agreement between the routinely used immunoassays is important for diagnosis and monitoring of thyroid disease. Efforts are continuously made to align the biochemical assays, and we aimed to evaluate the agreement between immunoassays used in a clinical laboratory setting among non-pregnant and pregnant adults. DESIGN: Cross-sectional study. PARTICIPANTS: Serum samples were obtained from 192 blood donors (non-pregnant adults) and from 86 pregnant women in the North Denmark Region with no known thyroid disease. MEASUREMENTS: Each sample was used for measurement of thyroid-stimulating hormone (TSH) with the routinely used automatic immunoassays in the regional Departments of Clinical Biochemistry (Alinity, Abbott Laboratories, Cobas, Roche Diagnostics, and Atellica, Siemens Healthineers) and reported as the median with 95% confidence interval (95% CI). RESULTS: In nonpregnant adults, the level of TSH was higher with Cobas and Atellica than with Alinity as reflected by median (Alinity: 1.39 mIU/L (95% CI: 1.30-1.51 mIU/L); Cobas: 1.57 mIU/L (95% CI: 1.48-1.75 mIU/L); Atellica: 1.74 mIU/L (95% CI: 1.61-1.83 mIU/L)). Similarly, a trend was seen towards higher median TSH with Cobas than with Alinity among pregnant women (Alinity: 1.90 mIU/L (95% CI: 1.37-2.82 mIU/L); Cobas: 2.33 mIU/L (95% CI: 1.69-3.62 mIU/L)). CONCLUSION: Results of thyroid function tests obtained with different immunoassays were not interchangeable when evaluated among pregnant and non-pregnant adults. The distinct differences are relevant for clinical decision making and emphasize the necessity of clinical laboratory information when different assays are used for diagnosis and monitoring of patients with thyroid disease.

Evaluation of critical parameters in the hollow-fibre system for tuberculosis: A case study of moxifloxacin.

AIMS: The hollow­fibre system for tuberculosis (HFS­TB) is a preclinical model qualified by the European Medicines Agency to underpin the anti­TB drug development process. It can mimic in vivo pharmacokinetic (PK)­pharmacodynamic (PD) attributes of selected antimicrobials, which could feed into in silico models to inform the design of clinical trials. However, historical data and published protocols are insufficient and omit key information to allow experiments to be reproducible. Therefore, in this work, we aim to optimize and standardize various HFS­TB operational procedures. METHODS: First, we characterized bacterial growth dynamics with different types of hollow­fibre cartridges, Mycobacterium tuberculosis strains and media. Second, we mimicked a moxifloxacin PK profile within hollow­fibre cartridges, in order to check drug­fibres compatibility. Lastly, we mimicked the moxifloxacin total plasma PK profile in human after once daily oral dose of 400 mg to assess PK­PD after different sampling methods, strains, cartridge size and bacterial adaptation periods before drug infusion into the system. RESULTS: We found that final bacterial load inside the HFS­TB was contingent on the studied variables. Besides, we demonstrated that drug­fibres compatibility tests are critical preliminary HFS­TB assays, which need to be properly reported. Lastly, we uncovered that the sampling method and bacterial adaptation period before drug infusion significantly impact actual experimental conclusions. CONCLUSION: Our data contribute to the necessary standardization of HFS­TB experiments, draw attention to multiple aspects of this preclinical model that should be considered when reporting novel results and warn about critical parameters in the HFS­TB currently overlooked.

Comparative Analysis of the Minimal information for studies of extracellular vesicles Guidelines: Advancements and Implications for Extracellular Vesicle Research.

In 2014, the International Society for Extracellular Vesicles (ISEV) introduced the Minimal Information for Studies of Extracellular Vesicles (MISEV) guidelines to establish standards for extracellular vesicle (EV) research. These guidelines aimed to enhance reliability and reproducibility, addressing the expanding field of EV science. EVs, membrane-bound particles released by cells, play crucial roles in intercellular communication and are potential biomarkers for various conditions. Over the years, the EV landscape witnessed a surge in publications, emphasizing their roles in cancer and immune modulation. In response, the MISEV guidelines underwent evolution, leading to the MISEV2018 update. This version, generated through community outreach, provided a comprehensive framework for EV research methodologies, emphasizing separation, characterization, reporting standards, and community engagement. The MISEV2018 guidelines reflected responsiveness to feedback, acknowledging the evolving EV research landscape. The guidelines served as a testament to the commitment of the scientific community to rigorous standards and the collective discernment of experts. The present article compares previous MISEV guidelines with its 2023 counterpart, highlighting advancements, changes, and impacts on EV research standardization. The 2023 guidelines build upon the 2018 principles, offering new recommendations for emerging areas. This comparative exploration contributes to understanding the transformative journey in EV research, emphasizing MISEV's pivotal role and the scientific community's adaptability to challenges.

Quantitative Metrics in Mass-Gathering Studies: A Comprehensive Systematic Review.

INTRODUCTION: Mass gatherings are events where many people come together at a specific location for a specific purpose, such as concerts, sports events, or religious gatherings, within a certain period of time. In mass-gathering studies, many rates and ratios are used to assess the demand for medical resources. Understanding such metrics is crucial for effective planning and intervention efforts. Therefore, this systematic review aims to investigate the usage of rates and ratios reported in mass-gathering studies. METHODS: In this systematic review, the PRISMA guidelines were followed. Articles published through December 2023 were searched on Web of Science, Scopus, Cochrane, and PubMed using the specified keywords. Subsequently, articles were screened based on titles, abstracts, and full texts to determine their eligibility for inclusion in the study. Finally, the articles that were related to the study's aim were evaluated. RESULTS: Out of 745 articles screened, 55 were deemed relevant for inclusion in the study. These included 45 original research articles, three special reports, three case presentations, two brief reports, one short paper, and one field report. A total of 15 metrics were identified, which were subsequently classified into three categories: assessment of population density, assessment of in-event health services, and assessment of out-of-event health services. CONCLUSION: The findings of this study revealed notable inconsistencies in the reporting of rates and ratios in mass-gathering studies. To address these inconsistencies and to standardize the information reported in mass-gathering studies, a Metrics and Essential Ratios for Gathering Events (MERGE) table was proposed. Future research should promote consistency in terminology and adopt standardized methods for presenting rates and ratios. This would not only enhance comparability but would also contribute to a more nuanced understanding of the dynamics associated with mass gatherings.

Cultural adaptation, validation, and standardization of a developmental screening tool (ASQ-3) in Iranian children.

Objectives: This study aimed at culturally adapting, validating, and standardizing the Ages and Stages Questionnaire, third edition (ASQ-3) by implementing a nation-wide cross-sectional methodological study in order to provide a valid and reliable tool for determining the developmental status of Iranian children. Materials & Methods: This cross-sectional and methodological study was conducted on Iranian children between 1-66 months. The ASQ-3 tool was translated; following that, its face and content validity, as well as the cross-cultural adaptation were assessed by 51 specialists and experts in the field of pediatrics and child development. In order to determine the reliability of the ASQ-3 (using Cronbach's alpha), and cut-off points. All statistical analyses were performed using STATA software. Results: This study was enrolled in 2 phases. The face and content validity, as well as the cultural relevance of the Persian version of ASQ-3 was confirmed using panel of specialists views then researchers investigated 11,740 children aged 1-66 months in order to evaluate the reliability of the tool. The Cronbach's alpha coefficients (reliability) determined for the ASQ-3 and the cut-off points for the ASQ-3 of different age groups and domains were determined by calculating one and two SDs below the mean; the latter represents the main cut-off point, and the interval between the two represents the monitoring zone according to the ASQ-3 technical manual. Conclusion: The results of this study showed that the Iranian version of ASQ-3 is valid and reliable; moreover, the cut-off points designated for it can be implemented in the Iranian children community to assess their developmental status.

A single workflow for multi-species blood transcriptomics.

BACKGROUND: Blood transcriptomic analysis is widely used to provide a detailed picture of a physiological state with potential outcomes for applications in diagnostics and monitoring of the immune response to vaccines. However, multi-species transcriptomic analysis is still a challenge from a technological point of view and a standardized workflow is urgently needed to allow interspecies comparisons. RESULTS: Here, we propose a single and complete total RNA-Seq workflow to generate reliable transcriptomic data from blood samples from humans and from animals typically used in preclinical models. Blood samples from a maximum of six individuals and four different species (rabbit, non-human primate, mouse and human) were extracted and sequenced in triplicates. The workflow was evaluated using different wet-lab and dry-lab criteria, including RNA quality and quantity, the library molarity, the number of raw sequencing reads, the Phred-score quality, the GC content, the performance of ribosomal-RNA and globin depletion, the presence of residual DNA, the strandness, the percentage of coding genes, the number of genes expressed, and the presence of saturation plateau in rarefaction curves. We identified key criteria and their associated thresholds to be achieved for validating the transcriptomic workflow. In this study, we also generated an automated analysis of the transcriptomic data that streamlines the validation of the dataset generated. CONCLUSIONS: Our study has developed an end-to-end workflow that should improve the standardization and the inter-species comparison in blood transcriptomics studies. In the context of vaccines and drug development, RNA sequencing data from preclinical models can be directly compared with clinical data and used to identify potential biomarkers of value to monitor safety and efficacy.

A novel approach to retrograde autologous priming for infant, pediatric and adult populations undergoing congenital heart surgery.

INTRODUCTION: Retrograde Autologous Priming (RAP) of cardiopulmonary bypass (CPB) circuits is an effective way to reduce prime volume, commonly through the transfer of prime into separate reservoirs or circuit manipulation. We describe a simple and safe technique for RAP without the need for any circuit modifications or manipulations. METHODS: For this technique, a separate roller pump for ultrafiltration (UF) is used. After adequate heparinization and arterial cannulation, the UF pump is initiated slowly, removing prime through the effluent of the UF, replacing with the patient's blood from the aortic cannula. Once the arterial line and UF circuit are autologous primed, the arterial head displaces reservoir crystalloid toward the UF circuit at a flow rate equal to the UF pump, displacing the crystalloid prime with blood from the UF circuit, autologous priming the boot and oxygenator with blood, crystalloid again being removed by the effluent. After venous cannulation, the venous line prime is replaced with autologous blood, the crystalloid removed by the effluent of the UF circuit via the arterial head. During RAP, if the patient becomes hypovolemic, either autologous volume is transfused back to the patient, or CPB is initiated, without the need for circuitry modifications. RESULTS: The patient population in this sample consisted of 63 patients ranging between 6.1 kg and 115.6 kg. The smaller the patient, the less blood volume available for RAP and therefore the less prime volume able to be removed. Overall percent removal increases as our patients size increases compared to total circuit volume. CONCLUSION: This RAP technique is a safe and effective way to achieve a standardized asanguinous prime for many regardless of patient or circuit size in the absence of contraindications such as low starting hematocrit, emergency surgery or physiologic instability. Most importantly, this potentially reduces the amount of hemodilution patients see from CPB initiation and therefore the lowest nadir hematocrit and consequently the amount of required homologous blood products needed during surgery.

World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonization Project: V. physical examination standards in endometriosis research.

OBJECTIVE: The World Endometriosis Research Foundation (WERF) established the Endometriosis Phenome and Biobanking Harmonisation Project (EPHect) to create standardized documentation tools (with common data elements) to facilitate the comparison and combination of data across different research sites and studies. In 2014, four data research standards were published: clinician-reported surgical data, patient-reported clinical data, and fluid and tissue biospecimen collection. Our current objective is to create an EPHect standard for the clinician-reported physical examination (EPHect-PE) for research studies. DESIGN: An international consortium involving 26 clinical and academic experts and patient partners from 11 countries representing 25 institutions and organizations. Two virtual workshops, followed by the development of the physical examination standards that underwent multiple rounds of iterations and revisions. SUBJECTS: N/A MAIN OUTCOME MEASURE(S): N/A RESULT(S): The EPHect physical examination (EPHect-PE) tool provides standardised assessment of physical examination characteristics and pain phenotyping. Data elements involve examination of a) back and pelvic girdle; b) abdomen including allodynia and trigger points; c) vulva including provoked vestibulodynia; d) pelvic floor muscle tone and tenderness; e) tenderness on unidigital pelvic exam; f) presence of pelvic nodularity; g) uterine size and mobility; h) presence of adnexal masses; i) presence of incisional masses; j) speculum examination; k) tenderness and allodynia at an extra-pelvic site (e.g. forearm); and l) recording of anthropometrics. CONCLUSION(S): The EPHect physical examination standards (EPHect-PE) will facilitate the standardised documentation of the physical examination, including the assessment and documentation of examination phenotyping of endometriosis-associated pelvic pain.