Background: Flow cytometry is not routinely performed in clinical laboratories for the diagnosis of classic Hodgkin lymphoma (CHL).
Methods: Fourteen cases of CHL and 132 cases of the control group were studied by 10-color flow cytometry, with markers including CD3, CD4, CD7, CD8, and CD26, as well as calculated parameters such as the CD4:CD8 ratio, percent CD3+CD4+CD26- T-cells of CD3+CD4+ T-cells, percent CD3+CD4+CD26- T-cells of total events, CD7 coefficient of variation among CD3+CD4+CD26- T-cells, and CD7 median fluorescence intensity of CD3+CD4+CD26- T-cells relative to CD3+CD8+ T-cells.
Results: CHL cases showed a median percent CD3+CD4+CD26- of CD3+CD4+ T-cells of 72.3% with range from 41.1% to 94.4%, median percent CD3+CD4+CD26- T-cells of total events of 17.4% with range from 4.6% to 52.5%, CD7 coefficient of variation among CD3+CD4+CD26- T-cells less than 100%, and CD7 median fluorescence intensity of CD3+CD4+CD26- T-cells relative to CD3+CD8+ T-cells of 1.7 with range from 0.4 to 3.5. In the control group, every entity showed some degree of overlap with CHL in terms of these parameters. A "Hodgkin score" was thus constructed to enhance separation of CHL from other entities. A threshold Hodgkin score of 15.35 achieved a sensitivity of 78.6% and specificity of 96.2% in the diagnosis of CHL. Incorporating the Hodgkin score into a simple algorithm raises the specificity to 100%.
Conclusion: In this study, we used flow cytometry to demonstrate increased CD3+CD4+CD26- T-cells in CHL, and derived a Hodgkin score for the diagnosis of CHL.
Aim: This study aimed to investigate the effects of 45S5 bioactive glass-ointment (BG) on cutaneous wound healing in rats at the molecular, biochemical, and histopathological levels.
Materials and methods: Thirty-two rats were divided into four groups (n = 8): Control, Sham, BG, and DEX (Dexpanthenol). While no wound treatment was applied to the CONTROL, a wound model was created in the Sham, and no treatment was applied. A wound model was created for other groups, and BG and DEX were applied locally for 21 days. During the 21-day experiment period, feed and water consumption and weight changes were observed. Wound areas were calculated on days 0, 3, 7, 4, and 21. Following treatment, the rats were euthanized and tissues from the wound area and blood samples were collected. While the expression levels of tumor necrosis factor-alpha (TNFα), Interleukin 6 (IL6), Interleukin 10 (IL10), transforming growth factor-beta (TGFβ), and vascular endothelial growth factor (VEGF) genes were determined by qPCR, the levels of TNFα, IL6, and IL10 proteins were measured by ELISA.
Results: It was observed that the BG group showed anti-inflammatory activity by suppressing TNFα levels and stimulating IL-10. In addition, it was determined that BG increased fibroblast activity and vascularization.
Conclusion: Current findings showed that topical application of BG has anti-inflammatory effects, while also accelerating healing by increasing vascularity and making positive contributions to tissue healing.
The treatment of multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB) is a formidable challenge. Treatment of MDR- and XDR-TB using bedaquiline (BDQ) and delamanid (DLM), two newly introduced medications, is steadily increasing. This narrative review aimed to present a concise overview of the existing information regarding BDQ and DLM, and elucidate their antimicrobial characteristics, resistance mechanisms, synergism with other drugs, and side effects.
To collect the required information about the antimicrobial properties, a search for scientific evidence from the Scopus, PubMed, and Embase databases was performed, and all recently published articles up to May 2024 were considered.
BDQ had potent antimicrobial effects on various types of nontuberculous mycobacteria (NTM), including rapid-growing and slow-growing species, and MDR/XDR Mycobacterium tuberculosis. The mechanisms of BDQ resistance in M. tuberculosis primarily involve mutations in three genes: atpE, mmpR (Rv0678) and pepQ. BDQ may have synergistic effects when combined with DLM, pyrazinamide, and pretomanid/linezolid. BDQ has a low incidence of side effects. The use of BDQ may prolong the QTc interval. Similarly, DLM showed potent antimicrobial effects on NTM and MDR/XDR M. tuberculosis. The main resistance mechanisms to DLM are induced by mutations in fbiA, fbiB, fbiC, fgd1, and ddn genes. The DLM had synergistic effects with BDQ and moxifloxacin. The DLM also has few side effects in some patients including QTc prolongation.
BDQ and DLM are suitable antibiotics with few side effects for the treatment of MDR/XDR-TB. These antibiotics have synergistic effects when combined with other antituberculosis drugs.
Background: In our recent publications, we reported the identification of three different molecular forms of total luteinizing hormone (LH) in urine, the intact LH, the free beta-subunit (LHβ), and its core fragment of LHβ (LHβcf), the latter two establishing the nonintact portion of LH. Following the discontinuation of the Delfia immunofluorometric assay (IFMA) (Wallac, PerkinElmer Finland, Finland), a leading method for detecting urinary LH for 30 years, this study seeks to assess the efficacy of three alternative commercial immunoassays in identifying various forms of U-LH.
Methods: Diluted urine samples underwent gel filtration to separate them into fractions, each containing different forms of LH. These were then assayed using Delfia IFMA, Architect LH (Abbott, USA), Elecsys LH Cobas (Roche, Switzerland), and Immulite 2000 LH (Siemens, Germany) immunoassays.
Results: Both Delfia and Immulite assays detected total U-LH, that is, all three forms of U-LH, including intact LH, LHβ, and LHβcf. Cobas detected only intact LH and LHβ, whereas Architect detected solely the intact LH.
Conclusions: Immulite assay can be an alternative tool to detect all forms of urinary LH, a feature likely to be instrumental in developing noninvasive, practical, and scalable solutions for evaluating total U-LH changes during minipuberty in neonates, during the onset of central puberty in peripubertal children, puberty-associated disorders in adolescents, and the fertility window in women, with a special focus on postpeak changes.
Neonatal jaundice (NNJ) affects a significant proportion of newborns globally, with an increased burden in low-resource settings. Effective health risk management of NNJ is hindered, particularly in resource-constrained environments, where early detection and treatment are challenging. The careSTART S1 Total Bilirubin Strip, a point-of-care testing (POCT) device based on a diazo-method, offers a potential solution by enabling onsite bilirubin measurement, thus, addressing the gap in early NNJ detection and management.
The current study evaluated the analytical performance of the careSTART S1 Total Bilirubin Strip for precision, linearity, method comparison, and lot-to-lot consistency following CLSI guidelines. For method comparison, 105 residual EDTA whole blood samples were analyzed with the careSTART S1 Total Bilirubin Strip and compared with reference measurements from the Roche Cobas c702 analyzer. Additionally, statistical analyses, including Passing-Bablok regression and Bland–Altman plots, were performed.
The careSTART S1 Total Bilirubin Strip showed allowable (<10%) within-laboratory imprecision of 2.5%–3.6% across all levels and demonstrated linearity over the range of 4.16–439.3 μmol/L. Method comparison revealed a constant negative bias with a mean bias −4.19 μmol/L. However, the 95% confidence interval (−7.10 to −1.28 μmol/L) of the bias is covered by the prespecified allowable bias of 8.3%, at medical decision point. Lot-to-lot variation ranged from 0.14%–6.49%, and was within the acceptable critical difference of 8.3%.
The careSTART S1 Total Bilirubin Strip provided accurate and reliable bilirubin measurements that could contribute to neonatal care in settings lacking central laboratory facilities.
Lower respiratory tract infection (LRTI) has long been an important threat to people's life and health, so the rapid diagnosis of LRTI is of great significance in clinical treatment. In recent years, the development of the sequencing technology provides a new direction for the rapid diagnosis of LRTI. In this review, the advantages and disadvantages of second-generation sequencing techniques represented by metagenomics next-generation sequencing (mNGS) and droplet digital polymerase chain reaction (ddPCR) in LRTI were reviewed. Furthermore, it offers insights into the future trajectory of this technology, highlighting its potential to revolutionise the field of respiratory infection diagnostics.
This review summarises developments in mechanistic research of second-generation sequencing technology their relationship with clinical practice, providing insights for future research.
Authors conducted a search on PubMed and Web of Science using the professional terms ‘Lower respiratory tract infection’ and ‘droplet digital polymerase chain reaction’ and ‘metagenomics next generation sequencing’. The obtained literature was then roughly categorised based on their research content. Similar studies were grouped into the same sections, and further searches were conducted based on the keywords of each section.
Different studies discussed the application of second-generation sequencing technology in LRTI from different angles, including the detection of pathogens of LRTI by mNGS and ddPCR, the prediction ability of drug-resistant bacteria, and comparison with traditional methods. We try to analyse the advantages and disadvantages of the second-generation sequencing technology by combing the research results of mNGS and ddPCR. In addition, the development direction of the second-generation sequencing technology is prospected.
This study evaluated the performance of the PCR-HRM assay by comparing it with immunohistochemistry (IHC) for mismatch repair (MMR) proteins and the PCR capillary electrophoresis (PCR-CE) methods.
A total of 224 patients with colorectal cancer participated in the study, with nearly half having mismatch repair deficiency (dMMR) tissues and the remainder possessing pMMR tissues. There was a 97.77% concordance between the PCR-HRM assay and IHC, and a 97.56% concordance between PCR-HRM and the PCR-CE assay. In comparison with IHC for dMMR proteins, the PCR-HRM demonstrated a sensitivity of 96.36% and a specificity of 99.12%. When juxtaposed with the PCR-CE assay, its sensitivity was 98.96% and specificity stood at 96.33%. The mutations observed in the microsatellite loci were uniformly distributed across all eight loci. Discrepant outcomes were more frequent in instances of MLH1 and PMS2 deficiency. Furthermore, the germline mutation status of MLH1, MSH2, PMS2, and MSH6 in 62 patients was ascertained using next-generation sequencing. All patients displaying MMR gene pathogenic mutations (N = 14) were identified as MSI-H by PCR-HRM, whereas those with MSS tissues (N = 43) did not exhibit MMR gene pathogenic mutations. Thus, the PCR-HRM method proficiently pinpoints tumors with verified germline MMR mutations, indicative of Lynch syndrome.
Conclusively, the PCR-HRM assay emerges as a swift and congruent diagnostic tool for microsatellite instability, boasting commendable sensitivity and specificity in colorectal cancer.
Alectinib is a second-generation anaplastic lymphoma kinase (ALK) inhibitor indicated for ALK-mutated non-small-cell lung cancer. Recently, the association between alectinib and red cell morphological abnormalities has been reported in a few case series. This retrospective observational study aims to determine the frequency of occurrence of acanthocytosis in patients taking alectinib and to evaluate the red cell indices, biochemical markers of haemolysis and eosin-5-maleimide (EMA) binding assay results in patients receiving alectinib.
Patients who were on alectinib and had a complete blood count test performed in Queen Elizabeth Hospital Haematology Laboratory between 1 May 2021 and 31 August 2021 were included in the study. Haematological investigations that had been performed before and after the commencement of alectinib were reviewed.
Fifty patients receiving alectinib were evaluated in this analysis. One hundred per cent of patients showed 3+ acanthocytes on the peripheral blood smears. Compared with the test results before starting alectinib, the post-alectinib blood tests showed a significantly lower haemoglobin concentration, red blood cell count and haematocrit; and a significantly higher mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration and red cell distribution width. All the tested patients showed a marked reduction in EMA mean channel fluorescence compared with normal control.
Our cohort revealed that alectinib caused significant acanthocytosis in all patients. Alectinib was also associated with changes in red cell indices and biochemical markers of haemolysis, compatible with a spherocytic and anisopoikilocytic morphology with haemolysis. Patients on alectinib had reduced EMA binding.
LIPA, situated on chromosome 10q23.2-q23.3, encodes the enzyme lysosomal acid lipase (LAL) (EC 3.1.1.13). Genetic alterations in LIPA lead to lysosomal acid lipase deficiency (LALD), an inborn error causing lipid metabolism anomalies and impairing cholesterol and triacylglyceride degradation. Over 40 LIPA variants have been documented, yet this study focuses on just two. The rs1051338 variant (NM_000235:c.46A>C) affects the signal peptide in Exon 2, whereas rs116928232, located in Exon 8, alters the splice site (NM_000235:c.894G>A), impacting lysosomal acid lipase activity. Considering the diverse clinical manifestations of LALD and the rising hepatic steatosis prevalence in Mexican population, mainly due to diet, these variants were investigated within this demographic to uncover potential contributing factors. This study aimed to reveal the frequency of rs1051338 and rs116928232 among healthy mestizo individuals in Northwest Mexico, marking a significant genetic exploration in this demographic.
Three hundred ten healthy mestizo individuals underwent PCR-RFLP analysis for both variants, and Sanger sequencing was performed for variant rs116928232. Bioinformatic analysis was also performed to predict protein changes.
Allele frequencies for rs1051338 (FA = 0.39, p value = 0.15) and rs116928232 (FA = 0.0016, p value = 0.49) aligned with reported data, while bioinformatic analysis allowed us to identify the protein alteration observed in both variants; finally, the variants showed no linkage between them (normalized D′ = 1.03, p value = 0.56).
Allelic frequencies closely matched reported data, and protein structure analysis confirmed variant impacts on LAL enzyme function. Notably, this study marks the first analysis of rs1051338 and rs116928232 in a healthy Mexican mestizo population.
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