Expanding the clinical spectrum of anti-IgLON5 disease: A multicenter retrospective study.

BACKGROUND: We conducted this study to describe detailed the clinical characteristics, ancillary test results and treatment response of a group of Chinese patients with anti-IgLON5 disease. METHODS: We recruited 13 patients with positive IgLON5 antibodies in serum and/or cerebrospinal fluid from nine tertiary referral centers. Patients were enrolled from February 2017 to July 2021. We retrospectively collected information on the presenting and main symptoms, treatment response and follow-up outcomes. RESULTS: The median age of onset for symptoms was 60 (range: 33-73) years and six of the 13 patients were females. The predominant clinical presentations included sleep disturbance (eight patients) and cognitive impairment (seven patients), followed by movement disorders (six patients). Parainfectious cause seemed plausible. Notably, we identified the first case of possible Epstein-Barr virus (EBV)-related anti-IgLON5 disease. Coexisting neural autoantibodies were identified in two patients. Furthermore, two patients had other autoimmune diseases. The IgG subclass was determined in four patients, including two with dominant IgG4 subtype and two with dominant IgG1 subtype. Additionally, 10 patients were treated with immunotherapy and four patients exhibited improvement. Overall, six of 10 patients for whom follow-up results were assessable had favorable clinical outcomes (modified Rankin Scale score ≤2). CONCLUSIONS: The clinical spectrum of anti-IgLON5 disease is variable. Our results highlight a boarder spectrum of anti-IgLON5 disease.

Development and implementation of an LIS-based validation system for autoverification toward zero defects in the automated reporting of laboratory test results.

BACKGROUND: Validation of the autoverification function is one of the critical steps to confirm its effectiveness before use. It is crucial to verify whether the programmed algorithm follows the expected logic and produces the expected results. This process has always relied on the assessment of human-machine consistency and is mostly a manually recorded and time-consuming activity with inherent subjectivity and arbitrariness that cannot guarantee a comprehensive, timely and continuous effectiveness evaluation of the autoverification function. To overcome these inherent limitations, we independently developed and implemented a laboratory information system (LIS)-based validation system for autoverification. METHODS: We developed a correctness verification and integrity validation method (hereinafter referred to as the "new method") in the form of a human-machine dialog. The system records personnel review steps and determines whether the human-machine review results are consistent. Laboratory personnel then analyze the reasons for any inconsistency according to system prompts, add to or modify rules, reverify, and finally improve the accuracy of autoverification. RESULTS: The validation system was successfully established and implemented. For a dataset consisting of 833 rules for 30 assays, 782 rules (93.87%) were successfully verified in the correctness verification phase, and 51 rules were deleted due to execution errors. In the integrity validation phase, 24 projects were easily verified, while the other 6 projects still required the additional rules or changes to the rule settings. Taking the Hepatitis B virus test as an example, from the setting of 65 rules to the automated releasing of 3000 reports, the validation time was reduced from 452 (manual verification) to 275 h (new method), a reduction in validation time of 177 h. Furthermore, 94.6% (168/182) of laboratory users believed the new method greatly reduced the workload, effectively controlled the report risk and felt satisfied. Since 2019, over 3.5 million reports have been automatically reviewed and issued without a single clinical complaint. CONCLUSION: To the best of our knowledge, this is the first report to realize autoverification validation as a human-machine interaction. The new method effectively controls the risks of autoverification, shortens time consumption, and improves the efficiency of laboratory verification.

Research and discussion on the evaluation scheme of reagent lot-to-lot differences in 16 chemiluminescence analytes, established by the EP26-A guidelines of the CLSI.

BACKGROUND: Verification of new reagent lots is a part of the crucial tasks in clinical laboratories. The Clinical and Laboratory Standards Institute (CLSI) EP26-A guideline provides laboratories with an evaluation method for reagent verification. The purpose of this study was to compare the performance of EP26-A with our laboratory reagent lot verification protocol and get the final scheme. METHOD: 16 chemiluminescence analytes including estradiol (E2), progesterone (P), ferritin (FER), cortisol (COR),carbohydrate antigen 153 (CA153), and free prostate-specific antigen (FPSA). were prospectively evaluated in two reagent lots. The laboratory's lot verification process included evaluating 5 patient samples with the current and new lots and acceptability according to a predefined criteria. For EP26-A, method imprecision data and critical differences at medical decision points were important factors affecting the sample size requirements and rejection limits. RESULT: The number of samples required for EP26-A was 3 to 12, of which P, CA153, and FPSA had increased by more than 5 samples compared with the current protocol. Of the 16 chemiluminescence analytes, 11 had higher rejection limits when using EP26-A than the current laboratory scheme. Our current protocol and EP26-A were in agreement in 32 of the 32 (100%) paired verifications. CONCLUSION: The EP26-A protocol is an important tool to find the differences between reagent lots, and it makes up for the loopholes in the statistical efficiency, sample concentration and quantity, and the selection of rejection limits in the current protocol.

Should quality goals be defined for multicenter laboratory testing? Lessons learned from a pilot survey on a national surveillance program for diabetes.

QUALITY PROBLEM: Robust laboratory protocols and stringent quality control (QC) procedures are essential for meaningful collection of data from multiple sites in large-scale population-based studies. Failure to design and implement an effective QC program not only adversely affects the scientific outcome, but also affects public confidence in the acceptability of the data. INITIAL ASSESSMENT: A pilot survey was conducted to assess the analytical performance of multicenter plasma glucose measurements in a national surveillance program for diabetes in China. CHOICE OF SOLUTION: Quality goals of the imprecision in terms of coefficient of variation (CV) and total analytical error (TEa) were defined based on the Clinical Laboratory Improvement Amendments (CLIA) criteria for acceptable performance of proficiency testing (PT) for plasma glucose using commercial QC preparations. IMPLEMENTATION: A web-based internal QC (IQC) program was established to monitor the analytical performance of the 302 centers participating in the survey. EVALUATION: The participation rate was 96% (289/302). Statistical analysis showed that the percentage of centers meeting the acceptable specifications of CV ≤5.0% and TEa ≤10% using the CLIA PT criteria was 91.7% while 76.4% of laboratories achieved the goals for desirable performance of CV ≤2.9% and TEa ≤6.9%, as proposed by the Laboratory Medicine Practice Guidelines for the management of diabetes mellitus based on biological criteria. LESSONS LEARNED: Communications and training are important in ensuring the data integrity of multicenter population-based studies. Performance verification and IQC programs should be implemented to help identify centers that can fulfill the eligibility criteria to perform laboratory analyses.

[Designing and implementation of a web-based quality monitoring system for plasma glucose measurement in multicenter population study].

OBJECTIVE: The aim of this paper is to describe the designing and implementation of a web-based plasma glucose measurement quality monitoring system to assess the analytical quality of plasma glucose measurements in multicenter population study and provide evidence for the future studies. METHODS: In the chronic non-communicable disease and related factor surveillance in China, a web based quality monitoring system for plasma glucose measurement was established to conduct evaluation on plasma glucose monitoring quality and effectiveness in 302 surveillance centers, including quality control data entry, transmission and feedback. RESULTS: The majority of the surveillance centers met the quality requirements and passed the evaluation of reproducibility and precision of plasma glucose measurement, only a few centers required intensive training and re-assessment. CONCLUSION: In order to ensure the completeness and reliability of plasma glucose measurement in the surveillance centers, the establishment of web-based plasma glucose measurement quality control system can facilitate the identification of the qualified surveillance centers and evaluation of plasma glucose measurement quality in different regions. Communication and training are important in ensuring plasma glucose measurement quality. It is necessary to further improve this web-based plasma glucose measurement quality monitoring system in the future to reduce the method specific plasma glucose measurement bias.