Multisystem Inflammatory Syndrome in Children and Cardiac Involvement: A Quaternary Center Experience.

We prospectively analyzed clinical and laboratory characteristics associated with cardiac involvement and severe presentation in multisystem inflammatory syndrome in children. Of 146 patients, 66 (45.2%) had cardiac dysfunction and 26 (17.8%) had coronary artery abnormalities. Lower serum albumin levels, absolute lymphocyte and platelet counts, and elevated ferritin, fibrinogen, d-dimer and interleukin-6 levels were associated with cardiac dysfunction. Possible treatment complications were identified.

Pressure-relief joints of initial support structural system used in tunnels with high-stress surrounding rock.

To address the problem of large deformations in weak surrounding rock tunnels under high ground stress, which cause damage to initial support structures, this study proposes a novel type of circumferential pressure-relief joint based on the concept of relieving deformation pressure of the surrounding rock. Key parameters of the pressure-relief joint, such as initial bearing capacity peak, constant bearing capacity, and allowable pressure-relief displacement, were obtained through numerical simulations and laboratory experiments. A comparison was made between the mechanical characteristics of rigid joints and the new type of pressure-relief joint. The applicability of the pressure-relief joint was verified through field tests, monitoring the surrounding rock pressure, internal forces in the steel frames, and the convergence displacement of the support structure. The results show that: (1) In the elastic stage, the stiffness of the new pressure-relief joint is similar to that of rigid joints. In the plastic stage, rigid joints fail directly, whereas the pressure-relief joint can control deformation and effectively release the deformation pressure of the surrounding rock while providing a constant bearing capacity. (2) The right arch foot in the experiment had poor rock quality, leading to high stress in the steel frame and significant horizontal displacement. After the deformation of the pressure-relief joint, the stress in the surrounding rock and steel frame significantly reduced, and the rate of horizontal deformation of the support structure slowed down. (3) The vertical and horizontal final displacements of the pressure-relief joint in the experiment were 61mm and 15mm, respectively, which did not exceed the allowable deformation values. The components of the support structure remained intact, ensuring safety. However, this study has limitations: the design of the new pressure-relief joint only allows for a vertical deformation of 150mm and a horizontal deformation of 50mm, limiting the range of pressure-relief deformation.

Within-laboratory reproducibility of Ames test results: Are repeat tests necessary?

The Ames test is required by regulatory agencies worldwide for assessing the mutagenic and carcinogenic potential of chemical compounds. This test uses several strains of bacteria to evaluate mutation induction: positive results in the assay are predictive of rodent carcinogenicity. As an initial step to understanding how well the assay may detect mutagens present as constituents of complex mixtures such as botanical extracts, a cross-sector working group examined the within-laboratory reproducibility of the Ames test using the extensive, publicly available National Toxicology Program (NTP) Ames test database comprising more than 3000 distinct test articles, most of which are individual chemicals. This study focused primarily on NTP tests conducted using the standard Organization for Economic Co-operation and Development Test Guideline 471 preincubation test protocol with 10% rat liver S9 for metabolic activation, although 30% rat S9 and 10 and 30% hamster liver S9 were also evaluated. The reproducibility of initial negative responses in all strains with and without 10% S9, was quite high, ranging from 95% to 99% with few exceptions. The within-laboratory reproducibility of initial positive responses for strains TA98 and TA100 with and without 10% rat liver S9 was ≥90%. Similar results were seen with hamster S9. As expected, the reproducibility of initial equivocal responses was lower, <50%. These results will provide context for determining the optimal design of recommended test protocols for use in screening both individual chemicals and complex mixtures, including botanicals.

Case mapping of geriatrics: Looking beyond age in skills laboratories.

BACKGROUND AND PURPOSE: Development of competencies related to care of older adults is necessary in pharmacy education. Skills laboratories as an essential part of the curriculum represent an important setting to teach geriatrics. The purpose of this research was to describe geriatrics cases in skills/simulation activities of an undergraduate pharmacy program. EDUCATIONAL ACTIVITY AND SETTING: A retrospective review of one academic year of skills laboratories from the pharmacy program at the Faculty of Pharmacy of University of Montreal was performed. Sessions including cases aged ≥65 years were selected. Content was extracted for characteristics relating to the patient, health, medications, and care context. A framework including geriatric considerations such as geriatric syndromes, frailty status, and potentially inappropriate medications was developed for data collection. FINDINGS: In total, 210 patient cases were extracted. Older adults (≥ 65 years) were represented in 51 cases (24%), with 8 cases (4%) aged ≥80 years. Geriatric syndromes were documented in 8%, functional status in 10%, and mobility in 12% of the cases. The median number of comorbidities and medications were 4 and 7, respectively. Regarding polypharmacy, only 10 cases had >10 medications, and none had >15 medications. Potentially inappropriate medications were found in 47% (n = 24) of the cases but were addressed in only 14% (n = 7) cases. SUMMARY: This mapping of skills laboratories highlights gaps in geriatrics content. Inclusion of the oldest patients and geriatrics issues were incorporated in a minority of cases and lacked many characteristics essential for geriatrics care.

Clinical epidemiology of adenovirus pneumonia among Chinese hospitalized children.

Adenovirus pneumonia is a prevalent form of community-acquired pneumonia among children. Research on the epidemiology and economic burden of this disease is crucial for public health, yet comprehensive data remains scarce, making it crucial to highlight on this topic. In this study, the data were extracted from the face sheet of discharge medical records collected from 26 tertiary children's hospitals from January 2016 to December 2021. In total, 1854 children with laboratory-confirmed adenovirus pneumonia were hospitalized, accounting for 0.13% of the total number of hospitalized for pneumonia in the database during the period. In addition, this figure represents a meager 0.027% when compared to the total number of hospitalized children. The male-to-female ratio was 1.78:1. The 1-3-year age group had the highest number of inpatients for adenoviral pneumonia and the largest proportion of the total hospitalizations in the same age group. Overall, winter is the primary season for the prevalence of adenovirus pneumonia, however, in southern China, there are two peak seasons, winter and summer. Although patients with 3/4 adenovirus pneumonia had no significant complications, some patients had complications such as respiratory failure, diarrhea, and myocardial damage. The median length of stay of adenovirus pneumonia was 8 d [interquartile range (IQR) 6-11], and the median hospitalization cost was 1293.83 United States dollars (IQR 811.81-2472.51). These valuable epidemiological insights into adenovirus pneumonia in Chinese children can help direct the development of targeted prevention and control strategies and surveillance measures for HAdV infections in this demographic.

Lung cancer tumor marker analysis: A clinical laboratory perspective.

 Clinical laboratories are responsible for performing lung cancer tumor marker testing as part of routine clinical care. It is their responsibility to guarantee that the reported tumor marker results are reliable and meet the necessary quality standards for proper clinical use. During the different laboratory phases, pre-analytical, analytical and post-analytical, specific steps and processes can introduce errors and generate incorrect clinical interpretation. This editorial briefly outlines critical laboratory issues related to lung cancer tumor markers, specific for each of these three laboratory phases.

Domain generalization across tumor types, laboratories, and species - Insights from the 2022 edition of the Mitosis Domain Generalization Challenge.

Recognition of mitotic figures in histologic tumor specimens is highly relevant to patient outcome assessment. This task is challenging for algorithms and human experts alike, with deterioration of algorithmic performance under shifts in image representations. Considerable covariate shifts occur when assessment is performed on different tumor types, images are acquired using different digitization devices, or specimens are produced in different laboratories. This observation motivated the inception of the 2022 challenge on MItosis Domain Generalization (MIDOG 2022). The challenge provided annotated histologic tumor images from six different domains and evaluated the algorithmic approaches for mitotic figure detection provided by nine challenge participants on ten independent domains. Ground truth for mitotic figure detection was established in two ways: a three-expert majority vote and an independent, immunohistochemistry-assisted set of labels. This work represents an overview of the challenge tasks, the algorithmic strategies employed by the participants, and potential factors contributing to their success. With an F1 score of 0.764 for the top-performing team, we summarize that domain generalization across various tumor domains is possible with today's deep learning-based recognition pipelines. However, we also found that domain characteristics not present in the training set (feline as new species, spindle cell shape as new morphology and a new scanner) led to small but significant decreases in performance. When assessed against the immunohistochemistry-assisted reference standard, all methods resulted in reduced recall scores, with only minor changes in the order of participants in the ranking.

Genetic sex validation for sample tracking in next-generation sequencing clinical testing.

OBJECTIVE: Data from DNA genotyping via a 96-SNP panel in a study of 25,015 clinical samples were utilized for quality control and tracking of sample identity in a clinical sequencing network. The study aimed to demonstrate the value of both the precise SNP tracking and the utility of the panel for predicting the sex-by-genotype of the participants, to identify possible sample mix-ups. RESULTS: Precise SNP tracking showed no sample swap errors within the clinical testing laboratories. In contrast, when comparing predicted sex-by-genotype to the provided sex on the test requisition, we identified 110 inconsistencies from 25,015 clinical samples (0.44%), that had occurred during sample collection or accessioning. The genetic sex predictions were confirmed using additional SNP sites in the sequencing data or high-density genotyping arrays. It was determined that discrepancies resulted from clerical errors (49.09%), samples from transgender participants (3.64%) and stem cell or bone marrow transplant patients (7.27%) along with undetermined sample mix-ups (40%) for which sample swaps occurred prior to arrival at genome centers, however the exact cause of the events at the sampling sites resulting in the mix-ups were not able to be determined.

PIK3CA testing in hormone receptor-positive/HER2-negative metastatic breast cancer: real-world data from Italian molecular pathology laboratories.

Introduction: PIK3CA gene mutations occur in approximately 40% of hormone receptor-positive/HER2-negative (HR+/HER2-) metastatic breast cancers (MBCs), electing them to targeted therapy. Testing PIK3CA status is complex due to selection of biological specimen and testing method. Materials & methods: This work investigates real-life experience on PIK3CA testing in HR+/HER2- MBC. Clinical, technical and molecular data on PIK3CA testing were collected from two referral laboratories. Additionally, the results of a nationwide PIK3CA survey involving 116 institutions were assessed. Results: Overall, n = 35 MBCs were PIK3CA-mutated, with mutations mostly occurring in exons 9 (n = 19; 51.4%) and 20 (n = 15; 40.5%). The nationwide survey revealed significant variability across laboratories in terms of sampling methodology, technical assessment and clinical report signing healthcare figures for PIK3CA molecular testing in diagnostic routine practice. Conclusion: This study provides insights into the real-world routine of PIK3CA testing in HR+/HER2- MBC and highlights the need for standardization and networking in predictive pathology.

Fatigue and vigilance in medical experts detecting breast cancer.

An abundance of laboratory-based experiments has described a vigilance decrement of reducing accuracy to detect targets with time on task, but there are few real-world studies, none of which have previously controlled the environment to control for bias. We describe accuracy in clinical practice for 360 experts who examined >1 million women's mammograms for signs of cancer, whilst controlling for potential biases. The vigilance decrement pattern was not observed. Instead, test accuracy improved over time, through a reduction in false alarms and an increase in speed, with no significant change in sensitivity. The multiple-decision model explains why experts miss targets in low prevalence settings through a change in decision threshold and search quit threshold and propose it should be adapted to explain these observed patterns of accuracy with time on task. What is typically thought of as standard and robust research findings in controlled laboratory settings may not directly apply to real-world environments and instead large, controlled studies in relevant environments are needed.

Factors affecting survival in patients undergoing percutaneous transhepatic biliary drainage for malignant biliary obstruction.

OBJECTIVE: The general approach to malignant biliary obstruction (MBO) is to provide drainage in all patients with jaundice. However, the procedure is often palliative, and its contribution to survival is debated. This study aimed to investigate prognostic factors in patients undergoing percutaneous transhepatic biliary drainage (PTBD) for MBO. PATIENTS AND METHODS: All laboratory values were divided into two groups based on median values: low and high. Chi-square analysis was performed for dichotomous data. The time from the PTBD procedure to the date of death or last follow-up was considered overall survival (OS). Univariate and multivariate analyses were calculated using the Cox regression model. RESULTS: A total of 152 patients were included in the study, of whom 84 (55.3%) were male. The median OS was 71 ± 12.6 days (95% CI: 46.3-95.7). The 1, 3, 6, and 12-month OS rates were 74.3%, 45.2%, 29.2%, and 13%, respectively. In the multivariate analysis, comorbidity (p=0.029), Eastern cooperative oncology group performance status (ECOG PS) (p=0.007), pre-PTBD albumin (p=0.025), post-PTBD aspartate aminotransferase (p=0.025), chemo naive (p<0.001), and post-PTBD chemotherapy (CT) (p=0.01) were found to be independent prognostic factors. CONCLUSIONS: In patients with poor prognosis MBO, the decision for PTBD should be made multidisciplinarily, taking into consideration ECOG PS, comorbidities, albumin levels, and prior CT status.

Text analysis framework for identifying mutations among non-small cell lung cancer patients from laboratory data.

BACKGROUND: Laboratory data can provide great value to support research aimed at reducing the incidence, prolonging survival and enhancing outcomes of cancer. Data is characterized by the information it carries and the format it holds. Data captured in Alberta's biomarker laboratory repository is free text, cluttered and rouge. Such data format limits its utility and prohibits broader adoption and research development. Text analysis for information extraction of unstructured data can change this and lead to more complete analyses. Previous work on extracting relevant information from free text, unstructured data employed Natural Language Processing (NLP), Machine Learning (ML), rule-based Information Extraction (IE) methods, or a hybrid combination between them. METHODS: In our study, text analysis was performed on Alberta Precision Laboratories data which consisted of 95,854 entries from the Southern Alberta Dataset (SAD) and 6944 entries from the Northern Alberta Dataset (NAD). The data covers all of Alberta and is completely population-based. Our proposed framework is built around rule-based IE methods. It incorporates topics such as Syntax and Lexical analyses to achieve deterministic extraction of data from biomarker laboratory data (i.e., Epidermal Growth Factor Receptor (EGFR) test results). Lexical analysis compromises of data cleaning and pre-processing, Rich Text Format text conversion into readable plain text format, and normalization and tokenization of text. The framework then passes the text into the Syntax analysis stage which includes the rule-based method of extracting relevant data. Rule-based patterns of the test result are identified, and a Context Free Grammar then generates the rules of information extraction. Finally, the results are linked with the Alberta Cancer Registry to support real-world cancer research studies. RESULTS: Of the original 5512 entries in the SAD dataset and 5017 entries in the NAD dataset which were filtered for EGFR, the framework yielded 5129 and 3388 extracted EGFR test results from the SAD and NAD datasets, respectively. An accuracy of 97.5% was achieved on a random sample of 362 tests. CONCLUSIONS: We presented a text analysis framework to extract specific information from unstructured clinical data. Our proposed framework has shown that it can successfully extract relevant information from EGFR test results.

Section E6.1-6.6 of the American College of Medical Genetics and Genomics (ACMG) Technical Laboratory Standards: Cytogenomic studies of acquired chromosomal abnormalities in neoplastic blood, bone marrow, and lymph nodes.

Cytogenomic analyses of acquired clonal chromosomal abnormalities in neoplastic blood, bone marrow, and/or lymph nodes are instrumental in the clinical management of patients with hematologic neoplasms. Cytogenetic analyses assist in the diagnosis of such disorders and can provide important prognostic information. Furthermore, cytogenetic studies can provide crucial information regarding specific genetically defined subtypes of these neoplasms that may have targeted therapies. At time of relapse, cytogenetic analysis can confirm recurrence of the original neoplasm, detect clonal disease evolution, or uncover a new unrelated neoplastic process. This section deals specifically with the technical standards applicable to cytogenomic studies of acquired clonal chromosomal abnormalities in neoplastic blood, bone marrow, and/or lymph nodes. This updated Section E6.1-6.6 supersedes the previous Section E6 in Section E: Clinical Cytogenetics of the American College of Medical Genetics and Genomics Technical Standards for Clinical Genetics Laboratories.

Quality control data management with unity real-time in molecular virology.

INTRODUCTION: Quality control (QC) is one component of an overarching quality management system (QMS) that aims at assuring laboratory quality and patient safety. QC data must be acceptable prior to reporting patients' results. Traditionally, QC statistics, records, and corrective actions were tracked at the Johns Hopkins Molecular Virology Laboratory using Microsoft Excel. Unity Real-Time (UnityRT), a QMS software (Bio-Rad Laboratories), which captures and analyzes QC data by instrument and control lot per assay, was implemented and its impact on the workflow was evaluated. The clinical utility of real-time QC monitoring using UnityRT is highlighted with a case of subtle QC trending of HIV-1 quantitative control results. METHODS: A comprehensive workflow analysis was performed, with a focus on Epstein Barr Virus (EBV) and BKV quantitative viral load testing (Roche cobas 6800). The number of QC steps and time to complete each step were assessed before and after implementing UnityRT. RESULTS: Our assessment of monthly QC data review revealed a total of 10 steps over 57 min when using Microsoft Excel, versus 6 steps over 11 min when using UnityRT. HIV-1 QC monitoring revealed subtle trending of the low positive control above the mean from November to December 2022, correlating with a change in the reagent kit lot. This associated with a shift in patients' results from positives below the lower limit of quantification to positives between 20 and 100 copies/mL. CONCLUSIONS: UnityRT consolidated QC analyses, monitoring, and tracking corrective actions. UnityRT was associated with significant time savings, which along with the interfaced feature of the QC capture and data analysis, have improved the workflow and reduced the risk of laboratory errors. The HIV-1 case revealed the value of the real-time monitoring of QC.

Section E6.7-6.12 of the American College of Medical Genetics and Genomics (ACMG) Technical Laboratory Standards: Cytogenomic studies of acquired chromosomal abnormalities in solid tumors.

Clinical cytogenomic studies of solid tumor samples are critical to the diagnosis, prognostication, and treatment selection for cancer patients. An overview of current cytogenomic techniques for solid tumor analysis is provided, including standards for sample preparation, clinical and technical considerations, and documentation of results. With the evolving technologies and their application in solid tumor analysis, these standards now include sequencing technology and optical genome mapping, in addition to the conventional cytogenomic methods, such as G-banded chromosome analysis, fluorescence in situ hybridization, and chromosomal microarray analysis. This updated Section E6.7-6.12 supersedes the previous Section E6.5-6.8 in Section E: Clinical Cytogenetics of the American College of Medical Genetics and Genomics Standards for Clinical Genetics Laboratories.

Cell block practices in European cytopathology laboratories.

BACKGROUND: There are numerous methods and procedures described for the preparation of cell blocks (CBs) from cytological samples. The objective of this study was to determine current practices and issues with CBs in European laboratories. METHODS: A link to an online survey, with 11 questions about CB practices, was distributed to cytology laboratories via participants of United Kingdom National External Quality Assurance Service for Cellular Pathology Techniques and national representatives in the European Federation of Cytology Societies. RESULTS: A total of 402 laboratories responded completely (337/402, 84%) or partially (65/402, 16%) to the survey by February 4, 2022. The most common CB practice is embedding cell pellets using plasma and thrombin (23.3%), agar (17.1%), Shandon/Epredia Cytoblock (11.4%), HistoGel (7.9%), and Cellient (3.5%). Other methods such as CytoFoam, albumin, gelatin, Cytomatrix, and collodion bags are rarely used (1.0%, 0.7%, 0.7%, 0.3%, and 0.2%, respectively). CBs are also prepared from naturally occurring clots or tissue fragments (29.5%) and cells scraped from unstained or prestained smears (4.4%). The most frequent issues with the CBs in a daily cytology practice are low cellularity (248/402, 62%) and dispersed cells (89/402, 22%), regardless of the CBs preparation method or how the samples for embedding were selected. CONCLUSIONS: There is a great variability in CB practices in European laboratories with low cellular CBs as the main issue. Additional studies are mandatory to evaluate and improve performance and cellular yield of CBs.

In-lab synthesized turn-off fluorescence sensor for estimation of Gemigliptin and Rosuvastatin polypill appraised by Spider diagram, AGREE and whiteness metrics.

Gemigliptin-Rosuvastatin single-pill combination is a promising therapeutic tool in the effective control of hyperglycemia and hypercholesterolemia. Organic sensors with high quantum yields have profoundly significant applications in the pharmaceutical industry, such as routine quality control of marketed formulations. Herein, the fluorescence sensor, 2-Morpholino-4,6-dimethyl nicotinonitrile 3, (λex; 226 nm, λem; 406 nm), was synthesized with a fluorescence quantum yield of 56.86% and fully characterized in our laboratory. This sensor showed high efficiency for the determination of Gemigliptin (GEM) and Rosuvastatin (RSV) traces through their stoichiometric interactions and simultaneously fractionated by selective solvation. The interaction between the stated analytes and sensor 3 was a quenching effect. Various experimental parameters and the turn-off mechanism were addressed. The adopted approach fulfilled the ICH validation criteria and showed linear satisfactory ranges, 0.2-2 and 0.1-1 µg/mL for GEM and RSV, respectively with nano-limits of detection less than 30 ng/mL for both analytes. The synthesized sensor has been successfully applied for GEM and RSV co-assessment in their synthetic polypill with excellent % recoveries of 98.83 ± 0.86 and 100.19 ± 0.64, respectively. No statistically significant difference between the results of the proposed and reported spectrophotometric methods in terms of the F- and t-tests. Ecological and whiteness appraisals of the proposed study were conducted via three novel approaches: the Greenness Index via Spider Diagram, the Analytical Greenness Metric, and the Red-Green-Blue 12 model. The aforementioned metrics proved the superiority of the adopted approach over the previously published one regarding eco-friendliness and sustainability. Our devised fluorimetric turn-off sensing method showed high sensitivity, selectivity, feasibility, and rapidity with minimal cost and environmental burden over other sophisticated techniques, making it reliable in quality control labs.

Creation of a microsurgical neuroanatomy laboratory and virtual operating room: a preliminary study.

OBJECTIVE: A comprehensive understanding of microsurgical neuroanatomy, familiarity with the operating room environment, patient positioning in relation to the surgery, and knowledge of surgical approaches is crucial in neurosurgical education. However, challenges such as limited patient exposure, heightened patient safety concerns, a decreased availability of surgical cases during training, and difficulties in accessing cadavers and laboratories have adversely impacted this education. Three-dimensional (3D) models and augmented reality (AR) applications can be utilized to depict the cortical and white matter anatomy of the brain, create virtual models of patient surgical positions, and simulate the operating room and neuroanatomy laboratory environment. Herein, the authors, who used a single application, aimed to demonstrate the creation of 3D models of anatomical cadaver dissections, surgical approaches, patient surgical positions, and operating room and laboratory designs as alternative educational materials for neurosurgical training. METHODS: A 3D modeling application (Scaniverse) was employed to generate 3D models of cadaveric brain specimens and surgical approaches using photogrammetry. It was also used to create virtual representations of the operating room and laboratory environment, as well as the surgical positions of patients, by utilizing light detection and ranging (LiDAR) sensor technology for accurate spatial mapping. These virtual models were then presented in AR for educational purposes. RESULTS: Virtual representations in three dimensions were created to depict cadaver specimens, surgical approaches, patient surgical positions, and the operating room and laboratory environment. These models offer the flexibility of rotation and movement in various planes for improved visualization and understanding. The operating room and laboratory environment were rendered in three dimensions to create a simulation that could be navigated using AR and mixed reality technology. Realistic cadaveric models with intricate details were showcased on internet-based platforms and AR platforms for enhanced visualization and learning. CONCLUSIONS: The utilization of this cost-effective, straightforward, and readily available approach to generate 3D models has the potential to enhance neuroanatomical and neurosurgical education. These digital models can be easily stored and shared via the internet, making them accessible to neurosurgeons worldwide for educational purposes.

A comprehensive stem cell laboratory module with blended learning for medical students at Tongji University.

The laboratory practice "Primary culture and directional differentiation of rat bone marrow mesenchymal stem cells (BMSCs)" is part of a required course for sophomore medical students at Tongji university, which has been conducted since 2012. Blended learning has been widely applied in medical courses. Based on a student-centered teaching philosophy, we reconstructed a comprehensive stem cell laboratory module with blended learning in 2021, aiming to facilitate students in enhancing their understanding of the multi-lineage differentiation potential of stem cells and improve their experimental skills, self-directed learning ability, and innovative thinking. First, we constructed in-depth online study resources, including videos demonstrating laboratory procedures, a PowerPoint slide deck, and published literature on student self-learning before class. In class, students performed a primary culture of BMSCs, freely chose among adipogenic, osteogenic, or chondrogenic differentiation, and used cytochemical or immunofluorescence staining for identification. After class, the extracurricular part involved performing quantitative polymerase chain reaction to examine the expression of multi-lineage differentiation marker genes, which was designed as an elective. After 2 years of practice, positive feedback was obtained from both students and faculty members who achieved, the learning goal as expected. The reconstructed stem cell laboratory module provides comprehensive practice opportunities for students. Students have a better understanding of BMSC at the molecular, cellular, and functional levels and have improved their experimental skills, which forms a basis for scientific research for medical students. Introducing blended learning into other medical laboratory practices thus seems valuable.

Healthcare center-based cell therapy laboratories supporting off-site manufactured cell therapies: The experiences of a single academic cell therapy laboratory.

BACKGROUND: Healthcare center-based cell therapy laboratories (HC CTLs) evolved from solely processing hematopoietic stem cells for transplantation to manufacturing various advanced cellular therapies. With increasing interest in cellular therapy applications, off-site manufactured products are becoming more common. HC CTLs play a critical role in supporting these products by shipping out cellular starting material (CSM) for further manufacturing and/or receiving, storing, and distributing final products. The experiences and challenges encountered by a single academic HC CTL in supporting these products are presented. METHODS: All off-site manufacturing protocols supported before 2023 were reviewed. Collected data included protocol characteristics (treatment indication, product type), process logistics (shipping, receiving, storage, thawing, distribution, documentation), and product handling volumes (CSM shipping and final product infusions). RESULTS: Between 2012 and 2022, 15 off-site manufactured cellular therapy early-phase, single- and multicenter clinical trials were supported. Trials were sponsored by academic/research and commercial entities. The number of protocols supported annually increased each year, with few ending. Products included cancer immunotherapies and gene therapies. Autologous CSM was collected and shipped, while autologous and allogeneic final products were received, stored, thawed, and distributed. Process differences among protocols included CSM shipping conditions, laboratory analyses, final product thaw conditions and procedures, number of treatments, and documentation. DISCUSSION: HC CTLs must contend with several challenges in supporting off-site manufacturing protocols. As demand for cellular therapies increases, stakeholders should collaborate from the early phases of clinical trials to streamline processes and standardize procedures to increase value, improve safety, and reduce the burden on HC CTLs.