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American Journal of Hematology Jul 2024Epstein Barr virus-positive (EBV+) diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS) is an aggressive B-cell lymphoma associated with EBV infection... (Review)
Review
DISEASE OVERVIEW
Epstein Barr virus-positive (EBV+) diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS) is an aggressive B-cell lymphoma associated with EBV infection included in the WHO classification of lymphoid neoplasms since 2016. Although historically associated to poor prognosis, outcomes seem to have improved in the era of chemoimmunotherapy.
DIAGNOSIS
The diagnosis is established through meticulous pathological evaluation. Detection of EBV-encoded RNA (EBER) is the standard diagnostic method. The ICC 2022 specifies EBV+ DLBCL, NOS as occurring when >80% of malignant cells express EBER, whereas the WHO-HAEM5 emphasizes that the majority of tumor cells should be EBER positive without setting a defined threshold. The differential diagnosis includes plasmablastic lymphoma, DLBCL associated with chronic inflammation, primary effusion lymphoma, among others.
RISK-STRATIFICATION
The International Prognostic Index (IPI) and the Oyama score can be used for risk-stratification. The Oyama score includes age >70 years and presence of B symptoms. The expression of CD30 and PD-1/PD-L1 are emerging as potential adverse but targetable biomarkers.
MANAGEMENT
Patients with EBV+ DLBCL, NOS, should be staged and managed following similar guidelines than patients with EBV-negative DLBCL. EBV+ DLBCL, NOS, however, might have a worse prognosis than EBV-negative DLBCL in the era of chemoimmunotherapy. Therefore, inclusion of patients in clinical trials when available is recommended. There is an opportunity to study and develop targeted therapy in the management of patients with EBV+ DLBCL, NOS.
PubMed: 38957951
DOI: 10.1002/ajh.27430 -
Journal of Materials Chemistry. B Jul 2024Paper-based analytical devices (PADs) are very convenient for determining biomarkers in point-of-care (POC) diagnosis while requiring sample pre-treatment or impurity...
Paper-based analytical devices (PADs) are very convenient for determining biomarkers in point-of-care (POC) diagnosis while requiring sample pre-treatment or impurity separation. This study reports a novel hydrogel-coupled, paper-based analytical device (PAD) for separation-free HO colorimetric detection in both aqueous solution and cell lysis with sample-to-answer analysis by directly loading into the sample test zone. By encapsulating an inorganic mimic enzyme and chromogenic substrate into the sodium alginate (SA) hydrogel, amplification of the color signal after catalyzing the substrate could be achieved. Taking advantage of the nanoscale porous structure of the hydrogel and the lateral flow channel of the PAD, large interference fragments or bio-macromolecules are prevented from diffusing into the chromogenic reaction, whereas the small target molecules enter the sensing region to trigger the catalytic reaction. This method demonstrated a rapid and accurate analysis with a limit of detection as low as 0.06 mM and detection selectivity. Our proposed device requires no enzyme and is separation-free, portable, easy-to-fabricate, and low-cost, and may offer a platform for quantitative or qualitative analysis of other analytes in body fluids for POC applications.
PubMed: 38957936
DOI: 10.1039/d4tb00715h -
International Journal of Chronic... 2024Chronic obstructive pulmonary disease (COPD) stands as a predominant cause of global morbidity and mortality. This study aims to elucidate the relationship between...
BACKGROUND
Chronic obstructive pulmonary disease (COPD) stands as a predominant cause of global morbidity and mortality. This study aims to elucidate the relationship between pyroptosis-related genes (PRGs) and COPD diagnosis in the context of immune infiltration, ultimately proposing a PRG-based diagnostic model for predicting COPD outcomes.
METHODS
Clinical data and PRGs of COPD patients were sourced from the GEO database. The "ConsensusClusterPlus" package was employed to generate molecular subtypes derived from PRGs that were identified through differential expression analysis and LASSO Cox analysis. A diagnostic signature including eight genes (CASP4, CASP5, ELANE, GPX4, NLRP1, GSDME, NOD1and IL18) was also constructed. Immune cell infiltration calculated by the ESTIMATE score, Stroma scores and Immune scores were also compared on the basis of pyroptosis-related molecular subtypes and the risk signature. We finally used qRT - PCR to detect the expression levels of eight genes in COPD patient and normal.
RESULTS
The diagnostic model, anchored on eight PRGs, underwent validation with an independent experimental cohort. The area under the receiver operating characteristic (ROC) curves (AUC) for the diagnostic model showcased values of 0.809, 0.765, and 0.956 for the GSE76925, GSE8545, and GSE5058 datasets, respectively. Distinct expression patterns and clinical attributes of PRGs were observed between the comparative groups, with functional analysis underscoring a disparity in immune-related functions between them.
CONCLUSION
In this study, we developed a potential as diagnostic biomarkers for COPD and have a significant role in modulating the immune response. Such insights pave the way for novel diagnostic and therapeutic strategies for COPD.
Topics: Humans; Pulmonary Disease, Chronic Obstructive; Pyroptosis; Databases, Genetic; Predictive Value of Tests; Gene Expression Profiling; Lung; Male; Female; Middle Aged; Genetic Markers; Case-Control Studies; Transcriptome; Aged; Reproducibility of Results; Genetic Predisposition to Disease; Prognosis
PubMed: 38957709
DOI: 10.2147/COPD.S438686 -
Dermatology Reports Jun 2024Deep cutaneous mycoses (DCMs) and skin fungal infections can cause significant morbidity until diagnosed and treated. In immunocompromised people, spp., spp., and...
Deep cutaneous mycoses (DCMs) and skin fungal infections can cause significant morbidity until diagnosed and treated. In immunocompromised people, spp., spp., and spp. fungi can cause these infections, but dermatophytes, especially and , are the most common. Superficial erythematous lesions become firm subcutaneous nodules, ulcers, abscesses, or sinus tracts. In advanced cases, DCMs can cause osteomyelitis and bone loss. DCM included mycetoma, a chronic infectious disease of the skin, subcutaneous tissues, and bones. In some areas, it is endemic and can mimic cutaneous tuberculosis or cancerous lesions, making diagnosis difficult. Clinical presentation, radiological findings, and microbiological culture are used to diagnose with molecular methods helping in culture-negative cases. An immunocompetent farmer with a wrist lesion initially suspected as cutaneous squamous cell carcinoma was histologically diagnosed as eumycetoma, emphasizing the importance of considering deep mycoses in high-risk individuals and their heterogeneous clinical presentation.
PubMed: 38957634
DOI: 10.4081/dr.2023.9782 -
Dermatology Reports Jun 2024In this case study, we describe a 21-year-old man with erythropoietic protoporphyria who sought medical attention in April 2022 for diffuse edema and erythema of the...
In this case study, we describe a 21-year-old man with erythropoietic protoporphyria who sought medical attention in April 2022 for diffuse edema and erythema of the hands. These symptoms had been present since childhood and usually occurred soon after sun exposure. The patient's medical history showed that chromosome 18's long arm had partially deleted. We performed a number of tests, including measuring total erythrocyte protoporphyrin levels and utilizing a spectrofluorometer to assess the fluorometric emission peak of plasma porphyrins, based on the patient's medical history and clinical symptoms. Furthermore, a genetic analysis identified an intronic variant on one allele, c.315-48T>C (IVS3-48T>C), which is categorized as a susceptibility polymorphism, and a complete deletion of the ferrochelatase gene on the other allele. The patient's clinical condition improved following the June 2022 afamelanotide implant procedure.
PubMed: 38957628
DOI: 10.4081/dr.2023.9784 -
Annals of Gastroenterological Surgery Jul 2024Crohn's disease (CD)-associated intestinal cancers are characterized by their high incidence, particularly at the anorectal site in the Japanese population. Accumulating...
BACKGROUND AND AIMS
Crohn's disease (CD)-associated intestinal cancers are characterized by their high incidence, particularly at the anorectal site in the Japanese population. Accumulating evidence revealed that younger-onset sporadic colorectal cancer may exhibit unique biological features. To the best of our knowledge, few previous articles reported clinicopathological features in patients with CD-associated anorectal cancer (CDAAC). Therefore, we aimed to clarify the relationship between the younger onset of cancer and clinicopathological characteristics and prognosis, and the efficacy of cancer surveillance in patients with CDAAC.
METHODS
CD patients who had been diagnosed with intestinal cancers from 1983 to 2020 were collected from 39 Japanese institutions in this study. Of 316 patients with CD-associated intestinal cancers, we analyzed 211 patients with CDAAC. We divided the patients into two groups according to the median age at cancer diagnosis (45 years old).
RESULTS
Younger-onset CDAAC (YO-CDAAC) patients were significantly more likely to have a poor outcome than those with older-onset CDAAC (OO-CDAAC) in terms of both disease-free survival (DFS) ( = 0.0014) and overall survival (OS) ( = 0.023). Multivariate analysis showed that age under 45 years old at diagnosis of cancer was one of the independent factors for poor DFS and OS (hazard ratios: 2.15, 95% confidence interval: 1.09-4.26, = 0.028, hazard ratios: 1.95, 95% confidence interval: 1.05-3.60, = 0.033, respectively). Patients detected via surveillance showed significantly better DFS and OS rates than symptomatic patients in YO-CDAAC ( = 0.012 and 0.0031, respectively).
CONCLUSIONS
YO-CDAAC may have a poorer prognosis compared with OO-CDAAC. Surveillance could be important to improve cancer prognosis, especially in young CD patients with anorectal disease.
PubMed: 38957565
DOI: 10.1002/ags3.12773 -
Frontiers in Immunology 2024Targeted therapy and immunotherapy are both important in the treatment of non-small-cell lung cancer (NSCLC). Accurate diagnose and precise treatment are key in...
Targeted therapy and immunotherapy are both important in the treatment of non-small-cell lung cancer (NSCLC). Accurate diagnose and precise treatment are key in achieving long survival of patients. fusion is a rare oncogenic factor, whose optimal detection and treatment are not well established. Here, we report on a 32-year-old female lung adenocarcinoma patient with positive PD-L1 and negative driver gene detected by DNA-based next-generation sequencing (NGS). A radical resection of the primary lesion after chemotherapy combined with PD-1 checkpoint inhibitor administration indicated primary immuno-resistance according to her pathological response and rapid relapse. A rare was detected by RNA-based NGS, which was confirmed by fluorescence hybridization. Multiplex immunofluorescence revealed a PD-L1 related heterogeneous immunosuppressive microenvironment with little distribution of CD4+ T cells and CD8+ T cells. Savolitinib therapy resulted in a progression-free survival (PFS) of >12 months, until a new secondary resistance mutation in p.D1228H was detected by re-biopsy and joint DNA-RNA-based NGS after disease progression. In this case, fusion NSCLC was primarily resistant to immunotherapy, sensitive to savolitinib, and developed secondary p.D1228H mutation after targeted treatment. DNA-RNA-based NGS is useful in the detection of such molecular events and tracking of secondary mutations in drug resistance. To this end, DNA-RNA-based NGS may be of better value in guiding precise diagnosis and individualized treatment in this patient population.
Topics: Humans; Female; Adenocarcinoma of Lung; Adult; Lung Neoplasms; High-Throughput Nucleotide Sequencing; Proto-Oncogene Proteins c-met; Oncogene Proteins, Fusion; Drug Resistance, Neoplasm; Immune Checkpoint Inhibitors
PubMed: 38957460
DOI: 10.3389/fimmu.2024.1386561 -
Journal of Hepatocellular Carcinoma 2024Long noncoding RNAs (lncRNAs) might be closely associated with hepatocellular carcinoma (HCC) progression and could serve as diagnostic and prognostic markers. This...
The Potential of the lncRNAs ADAMTSL4-AS1, AC067931 and SOCS2-AS1 in Peripheral Blood Mononuclear Cells as Novel Diagnostic Biomarkers for Hepatitis B Virus-Associated Hepatocellular Carcinoma.
PURPOSE
Long noncoding RNAs (lncRNAs) might be closely associated with hepatocellular carcinoma (HCC) progression and could serve as diagnostic and prognostic markers. This study aimed to investigate lncRNA-based diagnostic biomarkers for hepatitis B virus (HBV)-associated HCC.
MATERIALS AND METHODS
High-throughput transcriptome sequencing was conducted on the liver tissues of 15 patients with HBV-associated liver diseases (5 with chronic hepatitis B [CHB], 5 with liver cirrhosis [LC], and 5 with HCC). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to analyze lncRNA expressions. Potential diagnostic performance for HBV-associated HCC screening was evaluated.
RESULTS
Through trend analysis and functional analysis, we found that 8 lncRNAs were gradually upregulated and 1 lncRNA was progressively downregulated by regulation of target mRNAs and downstream HCC-associated signaling pathways. The validation of dysregulated lncRNAs in peripheral blood mononuclear cells (PBMCs) and HCC tissues by qRT-PCR revealed that ADAMTSL4-AS1, SOCS2-AS1, and AC067931 were significantly increased in HCC compared with CHB and cirrhosis. Moreover, differentially expressed lncRNAs were aberrantly elevated in Huh7, Hep3B, HepG2, and HepG2.215 cells compared with LX2 cells. Furthermore, ADAMTSL4-AS1, SOCS2-AS1, and AC067931 were identified as novel biomarkers for HBV-associated HCC. For distinguishing HCC from CHB, ADAMTSL4-AS1, AC067931, and SOCS2-AS1 combined with alpha-fetoprotein (AFP) had an area under the curve (AUC) of 0.945 (sensitivity, 83.9%; specificity, 89.8%). Similarly, for distinguishing HCC from LC, this combination had an AUC of 0.871 (sensitivity, 91.1%; specificity, 68.2%). Furthermore, this combination showed the highest diagnostic ability to distinguish HCC from CHB and LC (AUC, 0.905; sensitivity, 91.1%; specificity, 75.3%). In particular, this combination identified AFP-negative (AFP < 20 ng/mL) (AUC = 0.814), small (AUC = 0.909), and early stage (AUC = 0.863) tumors.
CONCLUSION
ADAMTSL4-AS1, SOCS2-AS1, and AC067931 combined with AFP in PBMCs may serve as a noninvasive diagnostic biomarker for HBV-associated HCC, especially AFP-negative, small, and early stage HCC.
PubMed: 38957436
DOI: 10.2147/JHC.S463804 -
Frontiers in Oncology 2024Microsatellite instability (MSI) is a genetic marker that is useful in the detection and treatment of Lynch syndrome (Sd). Although conventional techniques such as...
INTRODUCTION
Microsatellite instability (MSI) is a genetic marker that is useful in the detection and treatment of Lynch syndrome (Sd). Although conventional techniques such as immunohistochemistry (IHC) and polymerase chain reaction (PCR) are the standards for MSI detection, the advent of next-generation sequencing (NGS) has offered new possibilities, especially with circulating DNA.
CASE REPORT
We present the case of a 26-year-old patient with Lynch Sd and a -mutated metastatic colon cancer. The discordant MSI results between the conventional methods and NGS posed challenges in making treatment decisions. Subsequent NGS analysis revealed a high MSI status, leading to participation in an immunotherapy trial, with remarkable clinical response.
CONCLUSION
This case emphasizes the importance of comprehensive molecular profiling and strong interdisciplinary collaborations, especially in cases with ambiguous MSI results.
PubMed: 38957326
DOI: 10.3389/fonc.2024.1396869 -
Frontiers in Oncology 2024Lynch syndrome (LS) is an inherited cancer predisposition syndrome characterized by a high risk of colorectal and extracolonic tumors. Germline pathogenic variants (GPV)...
INTRODUCTION
Lynch syndrome (LS) is an inherited cancer predisposition syndrome characterized by a high risk of colorectal and extracolonic tumors. Germline pathogenic variants (GPV) in the gene are associated with <15% of all cases. The pseudogene presents high homology with , challenging molecular diagnosis by next-generation sequencing (NGS). Due to the high methodological complexity required to distinguish variants between and , most laboratories do not clearly report the origin of this molecular finding.
OBJECTIVE
The aim of this study was to confirm the GPVs detected by NGS in regions of high homology segments of the gene in a Brazilian sample.
METHODS
An orthogonal and gold standard long-range PCR (LR-PCR) methodology to separate variants detected in the gene from those detected in the pseudogene.
RESULTS
A total of 74 samples with a GPV detected by NGS in exons with high homology with pseudogene were evaluated. The most common was NM_000535.6:c.2182_2184delinsG, which was previously described as deleterious mutation in a study of African-American patients with LS and has been widely reported by laboratories as a pathogenic variant associated with the LS phenotype. Of all GPVs identified, only 6.8% were confirmed by LR-PCR. Conversely, more than 90% of GPV were not confirmed after LR-PCR, and the diagnosis of LS was ruled out by molecular mechanisms associated with
CONCLUSION
In conclusion, the use of LR-PCR was demonstrated to be a reliable approach for accurate molecular analysis of variants in segments with high homology with . We highlight that our laboratory is a pioneer in routine diagnostic complementation of the gene in Brazil, directly contributing to a more assertive molecular diagnosis and adequate genetic counseling for these patients and their families.
PubMed: 38957325
DOI: 10.3389/fonc.2024.1390221