Multisite studies for optimization of a highly efficient culture assay used for in vitro detection of residual undifferentiated human pluripotent stem cells intermingled in cell therapy products.

Introduction: MEASURE2 (Multisite Evaluation Study on Analytical Methods for Non-clinical Safety Assessment of HUman-derived REgenerative Medical Products 2) is a Japanese experimental public-private partnership initiative that aims to standardize testing methods for tumorigenicity evaluation of human pluripotent stem cell (hPSC)-derived cell therapy products (CTPs). MEASURE2 organized multisite studies to optimize the methodology of the highly efficient culture (HEC) assay, a sensitive culture-based in vitro assay for detecting residual undifferentiated hPSCs in CTPs. Methods: In these multisite studies, 1) the efficiency of colony formation by human induced pluripotent stem cells (hiPSCs) under two different culture conditions and 2) the sorting efficiency of microbeads conjugated to various anti-hPSC markers during hiPSC enrichment were evaluated using samples in which hiPSCs were spiked into hiPSC-derived mesenchymal stem cells. Results: The efficiency of colony formation was significantly higher under culture conditions with the combination of Chroman 1, Emricasan, Polyamines, and Trans-ISRIB (CEPT) than with Y-27632, which is widely used for the survival of hPSCs. Between-laboratory variance was also smaller under the condition with CEPT than with Y-27632. The sorting efficiency of microbeads conjugated with the anti-Tra-1-60 antibody was sufficiently higher (>80%) than those of the other various microbeads investigated. Conclusions: Results of these multisite studies are expected to contribute to improvements in the sensitivity and robustness of the HEC assay, as well as to the future standardization of the tumorigenicity risk assessment of hPSC-derived CTPs.

Joining forces for pathology diagnostics with AI assistance: The EMPAIA initiative.

Over the past decade, artificial intelligence (AI) methods in pathology have advanced substantially. However, integration into routine clinical practice has been slow due to numerous challenges, including technical and regulatory hurdles in translating research results into clinical diagnostic products and the lack of standardized interfaces. The open and vendor-neutral EMPAIA initiative addresses these challenges. Here, we provide an overview of EMPAIA's achievements and lessons learned. EMPAIA integrates various stakeholders of the pathology AI ecosystem, i.e., pathologists, computer scientists, and industry. In close collaboration, we developed technical interoperability standards, recommendations for AI testing and product development, and explainability methods. We implemented the modular and open-source EMPAIA Platform and successfully integrated 14 AI-based image analysis apps from eight different vendors, demonstrating how different apps can use a single standardized interface. We prioritized requirements and evaluated the use of AI in real clinical settings with 14 different pathology laboratories in Europe and Asia. In addition to technical developments, we created a forum for all stakeholders to share information and experiences on digital pathology and AI. Commercial, clinical, and academic stakeholders can now adopt EMPAIA's common open-source interfaces, providing a unique opportunity for large-scale standardization and streamlining of processes. Further efforts are needed to effectively and broadly establish AI assistance in routine laboratory use. To this end, a sustainable infrastructure, the non-profit association EMPAIA International, has been established to continue standardization and support broad implementation and advocacy for an AI-assisted digital pathology future.

Measurement of inward leakage of full-face masks in EN and ISO standards: comparison of gas and aerosol test agents.

In Europe, respiratory protective devices must be certified before they can be marketed. Among the parameters of interest, inward leakage (IL) characterizes the tightness between the face seal and the face, to verify that the device is well-designed. European standard EN 13274-1 (2001) and International Organization for Standardization (ISO) standard ISO 16900-1 (2019) specify that IL should be measured using sodium chloride (NaCl) aerosol or sulfur hexafluoride (SF6) gas. For reusable masks made of nonporous materials, both test agents are considered equally acceptable. However, the few studies that have compared IL values measured with various aerosols and gases have come to divergent conclusions. This work then aimed to measure IL with the test agents recommended by the standards to determine whether they are really equivalent. Since krypton (Kr) is an interesting candidate for replacing SF6 in standard tests, IL was assessed with SF6 and Kr simultaneously, and with NaCl aerosol using various calculation methods. Tests were carried out on 5 models of full-face masks donned on a headform connected to a breathing machine simulating 3 sinusoidal breathing rates of various intensities. The respirator fit on the headform was evaluated using a controlled negative pressure method to determine a manikin fit factor. Four scenarios were then tested to represent very poor, bad, good, and excellent fit. Gas concentration was measured using a mass spectrometer, and IL was calculated for SF6 and Kr. A combination of 3 devices allowed the determination of the number-based concentration of particles with diameters between 20 nm and 2 µm, and IL was calculated for each of the 33 channels, as well as using a cumulative number concentration. In addition, to comply with standards, a conversion was carried out to calculate IL using a cumulative mass concentration. The results of this work evidenced that the IL values measured with NaCl were systematically lower than those determined with gases. IL was also shown to vary with particle size, with a maximum value exceeding that calculated with cumulative concentrations (in number or mass). As part of the revision of the standards, protocols for measuring inward leakage should be redefined. On the one hand, acceptability thresholds should be re-evaluated according to the nature of the test agent (gas or aerosol), as it is clear that the 2 options do not give the same results for a given configuration. On the other hand, the aerosol leakage measurement protocol needs to be reworked to enable the measurement of a well-defined, robust, and reproducible inward leakage value.

Interactive Health Technology Tool for Kidney Living Donor Assessment to Standardize the Informed Consent Process: Usability and Qualitative Content Analysis.

BACKGROUND: Kidney living donation carries risks, yet standardized information provision regarding nephrectomy risks and psychological impacts for candidates remains lacking. OBJECTIVE: This study assesses the benefit of interactive health technology in improving the informed consent process for kidney living donation. METHODS: The Kidney Hub institutional open portal offers comprehensive information on kidney disease and donation. Individuals willing to start the kidney living donation process at Helsinki University Hospital (January 2019-January 2022) were invited to use the patient-tailored digital care path (Living Donor Digital Care Path) included in the Kidney Hub. This platform provides detailed donation process information and facilitates communication between health care professionals and patients. eHealth literacy was evaluated via the eHealth Literacy Scale (eHEALS), usability with the System Usability Scale (SUS), and system utility through Likert-scale surveys with scores of 1-5. Qualitative content analysis addressed an open-ended question. RESULTS: The Kidney Hub portal received over 8000 monthly visits, including to its sections on donation benefits (n=1629 views) and impact on donors' lives (n=4850 views). Of 127 living kidney donation candidates, 7 did not use Living Donor Digital Care Path. Users' ages ranged from 20 to 79 years, and they exchanged over 3500 messages. A total of 74 living donor candidates participated in the survey. Female candidates more commonly searched the internet about kidney donation (n=79 female candidates vs n=48 male candidates; P=.04). The mean eHEALS score correlated with internet use for health decisions (r=0.45; P<.001) and its importance (r=0.40; P=.01). Participants found that the Living Donor Digital Care Path was technically satisfactory (mean SUS score 4.4, SD 0.54) and useful but not pivotal in donation decision-making. Concerns focused on postsurgery coping for donors and recipients. CONCLUSIONS: Telemedicine effectively educates living kidney donor candidates on the donation process. The Living Donor Digital Care Path serves as a valuable eHealth tool, aiding clinicians in standardizing steps toward informed consent. TRIAL REGISTRATION: ClinicalTrials.gov NCT04791670; https://clinicaltrials.gov/study/NCT04791670. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2021-051166.

Roadmap towards safe and sustainable advanced and innovative materials. (Outlook for 2024-2030).

The adoption of innovative advanced materials holds vast potential, contingent upon addressing safety and sustainability concerns. The European Commission advocates the integration of Safe and Sustainable by Design (SSbD) principles early in the innovation process to streamline market introduction and mitigate costs. Within this framework, encompassing ecological, social, and economic factors is paramount. The NanoSafety Cluster (NSC) delineates key safety and sustainability areas, pinpointing unresolved issues and research gaps to steer the development of safe(r) materials. Leveraging FAIR data management and integration, alongside the alignment of regulatory aspects, fosters informed decision-making and innovation. Integrating circularity and sustainability mandates clear guidance, ensuring responsible innovation at every stage. Collaboration among stakeholders, anticipation of regulatory demands, and a commitment to sustainability are pivotal for translating SSbD into tangible advancements. Harmonizing standards and test guidelines, along with regulatory preparedness through an exchange platform, is imperative for governance and market readiness. By adhering to these principles, the effective and sustainable deployment of innovative materials can be realized, propelling positive transformation and societal acceptance.

Unified calibration of D-dimer can improve the uniformity of different detection systems.

Background: D-dimer at a low level is important evidence for excluding the onset and progression of thrombosis. It is readily detectable and yields rapid results, although significant variability exists among different detection systems. Our study aims to enhance the consistency across various detection systems. Methods: Twelve detection systems were included in our study. We sought to address this inconsistency by using various calibrators (two supplied by manufacturers and two comprising pooled human plasma diluted with different diluents) to standardize D-dimer measurements. We categorized the data into three groups according to D-dimer concentration levels: low (≤0.5 mg/L), medium (>0.5 mg/L - <3 mg/L), and high (≥3 mg/L). We then analyzed the data focusing on range, consistency, comparability, negative coincidence rate, and false negative rate. Results: Calibrating with pooled human plasma led to narrower result ranges in the low and medium groups (P < 0.05). In the low group, consistency improved from weak to strong (ICC 0.4-0.7, P﹤0.05), while it remained excellent in the other groups and overall (ICCï¹¥0.75, P﹤0.05). The percentage of pairwise comparability increased in both the low and high groups. Additionally, there was an increase in the negative coincidence rate. Conclusion: These findings demonstrate that uniform calibration of D-dimer can significantly enhance the consistency of results across different detection systems.

The shape of and applied weight on skin prick lancets critically affect the wheal size in the skin prick test.

The global application of the skin prick test (SPT) is attributed to the low costs, easy execution, and in vivo approach. Still, the healthcare professionals' technique and the lancet shape may challenge the standardization of the method. Thus, we investigated the influence of the shape of the lancet and the applied weight on the wheal size of SPT. Two allergic and one non-allergic individual were tested with allergens (Dermatophagoides pteronyssinus and Phleum pratense) and histamine solution (positive control), respectively. Horizontally (HS) and diagonally (DS) shouldered lancets with the same tip length (1 mm) were tested under two different conditions: either 60 g or 120 g weight pressure. The wheal size induced by the 4 different combinations was measured. The higher-weight device (120 g) induced a significantly larger and less variable wheal response with the tested allergens and histamine. However, the shape of the lancet affected the wheal size more than the applied weight. The least variable response was measured to histamine for the horizontal-shouldered lancet combined with the higher weight, whereas the same lancet with the lower weight resulted in a significant number of false negative results.

Evaluation and clinical application of a bracketing calibration-based isotope dilution liquid chromatography-tandem mass spectrometry candidate reference measurement procedure for serum theophylline.

A candidate reference measurement procedure (RMP) for serum theophylline via isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed. With a single-step precipitation pretreatment and a 6-min gradient elution, the method achieved baseline separation of theophylline and its analogs on a C18-packed column. A bracketing calibration method was used to ensure repeatable signal intensity and high measurement precision. The intra-assay and inter-assay imprecisions were 1.06%, 0.84%, 0.72% and 0.47%, 0.41%, 0.25% at concentrations of 4.22 µg/mL (23.40 µmol/L), 8.45 µg/mL (46.90 µmol/L), and 15.21 µg/mL (84.43 µmol/L), respectively. Recoveries ranged from 99.35 to 102.34%. The limit of detection (LoD) was 2 ng/mL, and the lowest limit of quantification (LLoQ) was 5 ng/mL. The linearity range extended from 0.47 to 60 µg/mL (2.61-333.04 µmol/L). No ion suppression and carry-over (< 0.68%) were observed. The relative bias for this candidate RMP that participated in 2023 External Quality Control for Reference Laboratories (RELA) conducted by the International Federation of Clinical Chemistry (IFCC) was within a range of 0.17 to 0.93%. Furthermore, two clinical immunoassay systems were compared with this candidate RMP, demonstrating good correlations. The results of the Trueness Verification Plan indicate significant differences among routine systems, highlighting the need for standardization efforts. The developed candidate RMP for serum theophylline serves as a precise reference baseline for standardizing clinical systems and assigning values to reference materials.

An International Study of Factors Affecting Variability of Dosimetry Calculations, Part 3: Contribution from Calculating Absorbed Dose from Time-Integrated Activity.

Image-based dosimetry-guided radiopharmaceutical therapy has the potential to personalize treatment by limiting toxicity to organs at risk and maximizing the therapeutic effect. The 177Lu dosimetry challenge of the Society of Nuclear Medicine and Molecular Imaging consisted of 5 tasks assessing the variability in the dosimetry workflow. The fifth task investigated the variability associated with the last step, dose conversion, of the dosimetry workflow on which this study is based. Methods: Reference variability was assessed by 2 medical physicists using different software, methods, and all possible combinations of input segmentation formats and time points as provided in the challenge. General descriptive statistics for absorbed dose values from the global submissions from participants were calculated, and variability was measured using the quartile coefficient of dispersion. Results: For the liver, which included lesions with high uptake, variabilities of up to 36% were found. The baseline analysis showed a variability of 29% in absorbed dose results for the liver from datasets where lesions included and excluded were grouped, indicating that variation in how lesions in normal liver were treated was a significant source of variability. For other organs and lesions, variability was within 7%, independently of software used except for the local deposition method. Conclusion: The choice of dosimetry method or software had a small contribution to the overall variability of dose estimates.

Golden spikes, scientific types, and the ma(r)king of deep time.

Chronostratigraphy is the subfield of geology that studies the relative age of rock strata and that aims at producing a hierarchical classification of (global) divisions of the historical time-rock record. The 'golden spike' or 'GSSP' approach is the cornerstone of contemporary chronostratigraphic methodology. It is also perplexing. Chronostratigraphers define each global time-rock boundary extremely locally, often by driving a gold-colored pin into an exposed rock section at a particular level. Moreover, they usually avoid rock sections that show any meaningful sign of paleontological disruption or geological discontinuity: the less obvious the boundary, the better. It has been argued that we can make sense of this practice of marking boundaries by comparing the status and function of golden spikes to that of other concrete, particular reference standards from other sciences: holotypes from biological taxonomy and measurement prototypes from the metrology of weight and measures. Alisa Bokulich (2020b) has argued that these 'scientific types' are in an important sense one of a kind: they have a common status and function. I will argue that this picture of high-level conceptual unity is mistaken and fails to consider the diversity of aims and purposes of standardization and classification across the sciences. I develop an alternative, disunified account of scientific types that shows how differences in ontological attitudes and epistemic aims inform scientists' choices between different kinds of scientific types. This perspective on scientific types helps to make sense of an intriguing mid-twentieth-century debate among chronostratigraphers about the very nature of their enterprise. Should chronostratigraphers conventionally make boundaries by designating golden spikes, or should they attempt to mark pre-existing 'natural' boundaries with the help of a different kind of scientific type?

Setting the Stage for Standardized Reporting of Clinical and Demographic Information in Laboratory-Based Studies of Hidradenitis Suppurativa.

Hidradenitis suppurativa (HS) is a complex inflammatory skin condition affecting 0.1-4% of the population that leads to permanent scarring in the axilla, inframammary region, groin, and buttocks. Its complex pathogenesis involves genetics, innate and adaptive immunity, microbiota, and environmental stimuli. Specific populations have a higher incidence of HS, including females and Black individuals and those with associated comorbidities. HS registries and biobanks have set standards for the documentation of clinical data in the context of clinical trials and outcomes research, but collection, documentation, and reporting of these important clinical and demographic variables are uncommon in HS laboratory research studies. Standardization in the laboratory setting is needed because it helps to elucidate the factors that contribute mechanistically to HS symptoms and pathophysiology. The purpose of this article is to begin to set the stage for standardized reporting in the laboratory setting. We discuss how clinical guidelines can inform laboratory research studies, and we highlight what additional information is necessary for the use of samples in the wet laboratory and interpretation of associated mechanistic data. Through standardized data collection and reporting, data harmonization between research studies will transform our understanding of HS and lead to novel discoveries that will positively impact patient care.

Exploring the Effectiveness of Hatha Yoga as a Complementary Treatment for Adolescent Idiopathic Scoliosis: Clinical Effect and Future Research Directions.

Adolescent idiopathic scoliosis (AIS) is a common spinal deformity that primarily affects adolescents during the key period of growth and development. While traditional treatment methods often involve bracing or surgery, Hatha yoga, a millennia-old practice rooted in Indian tradition, has emerged as a complementary option for AIS cases. This paper explores the potential benefits of Hatha yoga for adolescents with AIS. It also discusses the limitations of existing research, such as the lack of large-scale randomized controlled trials (RCTs), varying yoga protocols, and challenges in blinding participants and researchers. To address these limitations, I propose future research directions, including conducting large-scale RCTs, long-term follow-up studies, standardized yoga protocols, and assessing safety concerns. I also highlight the need for tailored interventions and comparative effectiveness studies to better understand the potential of Hatha yoga in the holistic treatment of AIS in adolescents.

A Standardized Nomenclature Design for Systematic Referencing and Identification of Animal Cellular Material.

The documentation, preservation and rescue of biological diversity increasingly uses living biological samples. Persistent associations between species, biosamples, such as tissues and cell lines, and the accompanying data are indispensable for using, exchanging and benefiting from these valuable materials. Explicit authentication of such biosamples by assigning unique and robust identifiers is therefore required to allow for unambiguous referencing, avoid identification conflicts and maintain reproducibility in research. A predefined nomenclature based on uniform rules would facilitate this process. However, such a nomenclature is currently lacking for animal biological material. We here present a first, standardized, human-readable nomenclature design, which is sufficient to generate unique and stable identifying names for animal cellular material with a focus on wildlife species. A species-specific human- and machine-readable syntax is included in the proposed standard naming scheme, allowing for the traceability of donated material and cultured cells, as well as data FAIRification. Only when it is consistently applied in the public domain, as publications and inter-institutional samples and data are exchanged, distributed and stored centrally, can the risks of misidentification and loss of traceability be mitigated. This innovative globally applicable identification system provides a standard for a sustainable structure for the long-term storage of animal bio-samples in cryobanks and hence facilitates current as well as future species conservation and biomedical research.

Standardization, Collaboration, and Education in the Implementation of Artificial Intelligence in Otolaryngology: The Key to Scalable Impact.

The study delves into the crucial role of standardization, collaboration, and education in the integration of artificial intelligence (AI) in otolaryngology. It emphasizes the necessity of large, diverse datasets for effective AI implementation in health care, particularly in otolaryngology, due to its reliance on medical imagery and diverse instruments. The text identifies current barriers, including siloed work in academia and sparse academic-industrial partnerships, while proposing solutions like forming interdisciplinary teams and aligning incentives. Moreover, it discusses the importance of standardizing AI projects through system reporting and advocates for AI education and literacy among otolaryngology practitioners.

Implementation of a pilot checklist for control standardization on fishery goods consignments at the Livorno border control post.

To standardize control activities, it is necessary to introduce checklists to support the control of consignments entering the European Union through border control posts (BCPs). This study aimed to develop a pilot checklist for the control of fishery consignments, preliminarily identified as the predominant group of goods entering the Livorno (Italy) BCP. The design of the pilot checklist was preceded by i) a revision of the current European and national legislation on the general and specific objectives of border control activities on fishery products and ii) a comparative analysis of two checklists (one of the Ministry of Health and one of the former Livorno border inspection post) developed on the basis of the repealed legislation. This comparison aimed to define the pilot checklist structure, verification objectives, and selection of assessment scores to be included in defining consignment compliance and acceptability. Once developed, the clarity and ease of use of the first draft of the pilot checklist were verified through its use in a field test during the control of 64 fishery product consignments. 22 regulatory sources (18 European and 4 national) were selected as reference legislation. The pilot checklist was structured as a dynamic "read-do" document based on the workflow of control activities described in the current legislation. The field test was useful in improving the clarity of the verification objectives within the documentary, identity, and physical control sections and in facilitating the use of the checklist and the collection of evidence during the control activity. This study, which focused on fishery products, can provide a practical approach for the development of checklists for all the other categories of goods under the responsibility of BCPs.

Diagnostics of IgE-mediated occupational allergies: Between reality, requirements, and opportunities.

Occupational skin and respiratory allergies are among the most common occupational diseases in Germany. The identification of the allergy trigger is essential for the recognition of an occupational allergy as well as for effective individual prevention. However, occupational type I allergens are among the "rare" allergens and the possibilities of guideline-compliant diagnosis using quality-tested skin test solutions is becoming increasingly difficult due to the reduction in commercially available test allergens. In order to guarantee meaningful diagnostic workup for all affected insured persons with suspected occupational type I allergies and to ensure this in the future, a durable optimization, standardization, and availability of allergy tests for occupational allergic diseases is urgently required. The need for action has been recognized by the German Social Accident Insurance (DGUV), and steps to eliminate the diagnostic gaps have been initiated by a joint research project at the Institute for Prevention and Occupational Medicine of the DGUV (IPA) and the Paul Ehrlich Institut (PEI). The evaluation of alternative methods for the production of standardized test allergen solutions can also be used for newly emerging allergens in the workplace. New allergen sources at workplaces and thus also sensitization and allergies among employees can be expected as a result of changes in work processes and the introduction of new technologies and/or working materials, which are also introduced in connection with climate change and the concept of sustainability.

[The Medical Informatics Initiative at a glance-establishing a health research data infrastructure in Germany]. / Die Medizininformatik-Initiative im Überblick ­ Aufbau einer Gesundheitsforschungsdateninfrastruktur in Deutschland.

The Medical Informatics Initiative (MII) funded by the Federal Ministry of Education and Research (BMBF) 2016-2027 is successfully laying the foundations for data-based medicine in Germany. As part of this funding, 51 new professorships, 21 junior research groups, and various new degree programs have been established to strengthen teaching, training, and continuing education in the field of medical informatics and to improve expertise in medical data sciences. A joint decentralized federated research data infrastructure encompassing the entire university medical center and its partners was created in the form of data integration centers (DIC) at all locations and the German Portal for Medical Research Data (FDPG) as a central access point. A modular core dataset (KDS) was defined and implemented for the secondary use of patient treatment data with consistent use of international standards (e.g., FHIR, SNOMED CT, and LOINC). An officially approved nationwide broad consent was introduced as the legal basis. The first data exports and data use projects have been carried out, embedded in an overarching usage policy and standardized contractual regulations. The further development of the MII health research data infrastructures within the cooperative framework of the Network of University Medicine (NUM) offers an excellent starting point for a German contribution to the upcoming European Health Data Space (EHDS), which opens opportunities for Germany as a medical research location.

[Expert consensus on standardized clinical applications of minimally invasive tooth extraction techniques].

Tooth extraction is a common and widely employed therapeutic procedure in oral and maxillofacial surgery. Minimally invasive tooth extraction can reduce both physical and psychological trauma to the patients, and is widely recommended as a first-line clinical treatment. But currently no guidelines or consensus has been available to provide a systematic introduction of minimally invasive tooth extraction to guide the clinical practices. To address this issue, this consensus, based on a comprehensive literature review and clinical experiences of experts, systematically summarizes the indications, target patients, and contraindications of minimally invasive tooth extraction, the overall workflow of this procedure (preoperative preparation, surgical steps, postoperative management, postoperative instructions, medications, and follow-up), and its common postoperative complications to provide a comprehensive guidance for clinical application of this technique.

State of the Art and Science of Immunocytochemistry.

BACKGROUND: Immunocytochemistry (ICC) is a widely available and extensively used ancillary method in diagnostic cytopathology with great variability in all test phases and a low level of adequate quality management. The non-standardized ICC landscape is now challenged with the introduction of the new European (EU) In Vitro Diagnostic Medical Devices Regulation (IVDR). According to this regulation, ICC on cytological slides falls under the category of Laboratory-Developed Tests (LDT), which requires rigorous standardization, validation, and thorough quality management. SUMMARY: Complete standardization of pre-analytical and analytical steps in ICC is impossible due to the complexity of the method and the constantly evolving antibodies, detection systems, and platforms. However, similar to the approach in immunohistochemistry, improving and standardizing "best practices" in quality management will result in high-quality, correct, accurate, and reliable ICC results. In this review, the current challenges of ICC in diagnostic cytopathology will be discussed, along with practical insights into ICC standardization and validation. KEY MESSAGES: Control slides prepared in the same manner as the patient samples, optimized ICC protocols, and participation in external quality control for ICC are the pillars of good quality management and essential to ensure safe and reliable patient diagnostics.

Standardization of the Norwood Procedure Improves Outcomes in a Medium-Sized Volume Center.

The Norwood operation has become common practice to palliate patients with hypoplastic left heart structures. Surgical technique and postoperative care have improved; yet, there remains significant attrition prior to stage II palliation. The objective of this study is to report outcomes before and after standardizing our approach to the Norwood operation. Patients who underwent the Norwood operation at Children's of Alabama were identified, those who underwent hybrid palliation operations were excluded. Pre- (2015-2020) and post- (2020-January 2023) standardization groups were compared and outcomes analyzed. Ninety-one patients were included (pre-standardization 44 (48.3%) and 47 (51.7%) post-standardization). There were no differences in baseline and intraoperative characteristics at Norwood between the pre- and post-standardization groups. Compared with pre-standardization, post-standardization was associated with decreased time to extubation (OR 0.87, 95%CI 0.79-0.96), inotrope duration (OR 0.92, 95%CI 0.86-0.98) and hospital length of stay (OR 0.98, 95%CI 0.96-0.99). There was a trend toward decreased cardiac arrest, reintervention rates, and interstage mortality for the post-standardization group. A standardized approach to complex neonatal cardiac operations such as the Norwood procedure may improve morbidity and decrease hospital resource utilization. We recommend establishing protocols at an institutional level to optimize outcomes in such high-risk patient populations.