RESUMEN
Background: As the number of long-term survivors of solid cancers keeps increasing, risk assessment of secondary hematologic malignancies is important for the prognosis of the patient. Germline genetic predisposition to secondary hematologic malignancy has been studied widely in myeloid neoplasms and rarely in lymphoid neoplasms. This study aimed to profile the mutational spectrums of patients with subsequent lymphoid tissue neoplasm to shed some light on the understudied area. Methods: In total, 39 patients who had primary solid cancer and subsequent hematologic malignancies were enrolled. We performed two next-generation sequencing (NGS) panel tests encompassing hereditary cancer predisposition genes and genes related to clonal hematopoiesis of indeterminate potential (CHIP). All statistical analyses were performed using R 3.5.1. Results: We found 8 of 39 patients with germline mutations in cancer predisposition genes; 4 of 18 patients had therapy-related myeloid neoplasms (22.2%); and 4 of 15 patients had secondary lymphoid malignancies (26.7%). Notably, of 14 patients who initially suffered from thyroid cancer, 5 patients (35.7%) had germline mutations. Malignancy of lymphoid tissue showed no association with radioactive iodine therapy but was observed to a greater extent in germline mutation-positive thyroid cancer patients regardless of their history of treatment. We observed that 24 of 39 patients (61.5%) were CHIP carriers. Patients who had secondary lymphoid malignancy were less likely to have CHIP than those who had myeloid malignancy. Conclusions: In patients with primary solid cancer who are planning to undergo cytotoxic chemotherapy, radiotherapy, or radioactive iodine therapy, an initial assessment with germline mutation testing using an expanded NGS panel, including low, moderate, and high-risk cancer-associated genes, and somatic CHIP mutation testing can screen the patients who are at risk of developing therapy-related myeloid and lymphoid malignancies. Through careful screening and monitoring throughout the treatment process, patients can benefit from the early detection of secondary malignancies and receive proper treatment.
RESUMEN
BACKGROUND: Automated cellular analyzers are expected to improve the analytical performance in body fluid (BF) analysis. We evaluated the analytical performance of three automated cellular analyzers and established optimum reflex analysis guidelines. METHODS: A total of 542 BF samples (88 cerebrospinal fluid [CSF] samples and 454 non-CSF samples) were examined using manual counting and three automated cellular analyzers: UniCel DxH 800 (Beckman Coulter), XN-350 (Sysmex), and UF-5000 (Sysmex). Additionally, 2,779 BF analysis results were retrospectively reviewed. For malignant cell analysis, the receiver operating characteristic (ROC) curve was used, and the detection of high fluorescence-BF cells (HF-BFs) using the XN-350 analyzer was compared with cytology results. RESULTS: All three analyzers showed good agreement for total nucleated cell (TNC) and red blood cell (RBC) counts, except for the RBC count in CSF samples using the UniCel DxH 800. However, variable degrees of differences were observed during differential cell counting. For malignant cell analysis, the area under the curve was 0.63 for the XN-350 analyzer and 0.76 for manual counting. We established our own reflex analysis guidelines as follows: HF-BFs <0.7/100 white blood cells (WBCs) is the criterion for quick scans with 100× magnification microscopic examination as a rule-out cut-off, while HF-BFs >83.4/100 WBCs or eosinophils >3.8% are the criteria for mandatory double check confirmation with 1,000× magnification examination. CONCLUSIONS: The three automated analyzers showed good analytical performances. Application of reflex analysis guidelines is recommended for eosinophils and HF-BFs, and manual confirmation is warranted.
Asunto(s)
Líquidos Corporales/citología , Recuento de Células/métodos , Área Bajo la Curva , Automatización , Recuento de Células/instrumentación , Citometría de Flujo , Humanos , Límite de Detección , Curva ROC , Reproducibilidad de los ResultadosRESUMEN
PURPOSE: Testing for autoantibodies to extractable nuclear antigens (ENAs) plays an important role in the diagnosis and management of systemic rheumatic disease. Currently, no gold standard tests are available for detecting anti-ENAs. To address this gap, we aimed to identify an assay that exhibits satisfactory diagnostic performance in the detection of five common anti-ENAs by comparing two commonly used assays, an automated fluorescent enzyme immunoassay (FEIA) and a microplate ELISA assay. MATERIALS AND METHODS: Sera from 100 patients with systemic rheumatic disease were collected and assayed with FEIA and microplate ELISA to detect anti-ENAs. Statistical analyses were performed to check the agreement rate between the two platforms using kappa coefficients. Analytical sensitivity and specificity for each assay were calculated. RESULTS: The concordance rates between ELISA and FEIA ranged from 89% for anti-RNP to 97% for anti-Scl-70, and the kappa coefficients of the two assays were in the range of 0.44 to 0.82. Between the two assays, a significant difference in sensitivity and specificity was seen only for anti-Sm and anti-RNP, respectively. CONCLUSION: In this study, FEIA and ELISA showed comparable efficiency for detecting anti-ENAs.
Asunto(s)
Antígenos Nucleares/metabolismo , Inmunoensayo/métodos , Enfermedades Reumáticas/inmunología , Adulto , Anticuerpos Antinucleares/sangre , Anticuerpos Antinucleares/metabolismo , Antígenos Nucleares/sangre , Ensayo de Inmunoadsorción Enzimática , Femenino , Fluorescencia , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Reumáticas/sangre , Enfermedades Reumáticas/diagnóstico , Sensibilidad y EspecificidadRESUMEN
Background: A positive relationship between testosterone level and nonalcoholic fatty liver disease (NAFLD) in women has been reported, but findings concerning the association are conflicting and inconclusive. Materials and Methods: We examined the association between testosterone level and the risk of NAFLD after stratification by menopausal status in 613 women (223 premenopausal women aged 21-52 years and 390 postmenopausal women aged 46-75 years). A diagnosis of fatty liver was based on abdominal ultrasonography. The odds ratios (ORs) and 95% confidence intervals (95% CIs) for NAFLD with 1 nmol/L increment in the log testosterone concentration were calculated after adjusting for confounding variables using multiple logistic regression analysis. Results: The prevalence of NAFLD was 19.2% among premenopausal women and 33.3% among postmenopausal women. After adjusting for age, regular exercise, type 2 diabetes, body mass index, mean arterial pressure, fasting plasma glucose, triglyceride, and high-density lipoprotein cholesterol, and testosterone levels, the OR (95% CI) for NAFLD was 2.79 (1.11-7.08) with 1 nmol/L increment of the log testosterone concentration in premenopausal women. However, these positive associations were not found in postmenopausal women after adjusting for the same covariables. Conclusion: Serum testosterone level was positively associated with NAFLD in premenopausal women but not in postmenopausal women. Our findings suggest that higher androgenic activity may be at least partly involved in the pathogenesis of NAFLD, particularly in premenopausal women.