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Frontiers in Oncology 2024Fluorescence hybridization (FISH) is an essential ancillary study used to identify clinically aggressive subsets of large B-cell lymphomas that have , or...
INTRODUCTION
Fluorescence hybridization (FISH) is an essential ancillary study used to identify clinically aggressive subsets of large B-cell lymphomas that have , or rearrangements. Small-volume biopsies such as fine needle aspiration biopsy (FNAB) and core needle biopsy (CNB) are increasingly used to diagnose lymphoma and obtain material for ancillary studies such as FISH. However, the performance of FISH in small biopsies has not been thoroughly evaluated or compared to surgical biopsies.
METHODS
We describe the results of and FISH in a series of 222 biopsy specimens, including FNAB with cell blocks, CNBs, and surgical excisional or incisional biopsies from 208 unique patients aggregated from 6 academic medical centers. A subset of patients had FNAB followed by a surgical biopsy (either CNB or excisional biopsy) obtained from the same or contiguous anatomic site as part of the same clinical workup; FISH results were compared for these paired specimens.
RESULTS
FISH had a low hybridization failure rate of around 1% across all specimen types. FISH identified concurrent and rearrangements in 20 of 197 (10%) specimens and concurrent and rearrangements in 3 of 182 (1.6%) specimens. The paired FNAB and surgical biopsy specimens did not show any discrepancies for or FISH; of the 17 patients with 34 paired cytology and surgical specimens, only 2 of the 49 FISH probes compared (4% of all comparisons) showed any discrepancy and both were at the locus. One discrepancy was due to necrosis of the CNB specimen causing a false negative FISH result when compared to the FNAB cell block that demonstrated a rearrangement.
DISCUSSION
FISH showed a similar hybridization failure rate in all biopsy types. Ultimately, , or FISH showed 96% concordance when compared across paired cytology and surgical specimens, suggesting FNAB with cell block is equivalent to other biopsy alternatives for evaluation of DLBCL or HGBCL FISH testing.
PubMed: 38903717
DOI: 10.3389/fonc.2024.1408238 -
Cureus May 2024Foreign workers comprise a significant portion of Singapore's workforce. They face multiple challenges when working there. A hand injury may add to these stressors,...
INTRODUCTION
Foreign workers comprise a significant portion of Singapore's workforce. They face multiple challenges when working there. A hand injury may add to these stressors, causing profound psychological and social impact. There are few studies in the literature that have analyzed this effect. The primary objective of this study, the first of its kind in Singapore, is to investigate the psychological impact and functional outcomes of hand injuries among foreign workers. By assessing the prevalence of psychological conditions such as stress, anxiety, and depression, along with measuring functional impairment using validated tools, this study aims to provide insights into the psycho-social challenges faced by this vulnerable population.
METHODS
A single-encounter interview was conducted for eligible patients. Psychological impact was measured using the DASS-21, symptom severity and function with the QuickDASH, and pain with the VAS. Injury-specific and demographic data were also collected. The Mann-Whitney U test and the Chi-Squared test were applied for non-parametric variables and categorical data, respectively. The adjusted p-value was <0.05.
RESULTS
Eighty foreign workers were recruited. The mean age was 33 years, and the median age was 31.5 years (28.2 to 37.0). The majority were male (97.5%), married (60%), and had a salary of less than SGD1500 (USD1077) per month (81.3%). The most common mechanism of injury was penetrating (60%, n=48). Stress, anxiety, and depression were positively associated with limitations in daily function. Multivariate analysis found that limitations in daily function were independently associated with stress, anxiety, and depression, regardless of hand dominance. Conclusion: This study has shown a significant psychological and social impact of hand injuries among foreign workers in Singapore. There is potential for the development of screening and support programs for at-risk workers to cater to their mental well-being. We recommend that the psychological impact of hand injuries be factored into holistic management and rehabilitation with adequate time and resource allocation. An ancillary benefit is the improvement of productivity and overall contribution to Singapore's economy.
PubMed: 38903327
DOI: 10.7759/cureus.60772 -
Scientific Reports Jun 2024This study probes the utility of biomarkers for microsatellite instability (MSI) detection and elucidates the molecular dynamics propelling colorectal cancer (CRC)...
This study probes the utility of biomarkers for microsatellite instability (MSI) detection and elucidates the molecular dynamics propelling colorectal cancer (CRC) progression. We synthesized a primer panel targeting 725 MSI loci, informed by The Cancer Genome Atlas (TCGA) and ancillary databases, to construct an amplicon library for next-generation sequencing (NGS). K-means clustering facilitated the distillation of 8 prime MSI loci, including activin A receptor type 2A (ACVR2A). Subsequently, we explored ACVR2A's influence on CRC advancement through in vivo tumor experiments and hematoxylin-eosin (HE) staining. Transwell assays gauged ACVR2A's role in CRC cell migration and invasion, while colony formation assays appraised cell proliferation. Western blotting illuminated the impact of ACVR2A suppression on CRC's PI3K/AKT/mTOR pathway protein expressions under hypoxia. Additionally, ACVR2A's influence on CRC-induced angiogenesis was quantified via angiogenesis assays. K-means clustering of NGS data pinpointed 32 MSI loci specific to tumor and DNA mismatch repair deficiency (dMMR) tissues. ACVR2A emerged as a pivotal biomarker, discerning MSI-H tissues with 90.97% sensitivity. A curated 8-loci set demonstrated 100% sensitivity and specificity for MSI-H detection in CRC. In vitro analyses corroborated ACVR2A's critical role, revealing its suppression of CRC proliferation, migration, and invasion. Moreover, ACVR2A inhibition under CRC-induced hypoxia markedly escalated MMP3, CyclinA, CyclinD1, and HIF1α protein expressions, alongside angiogenesis, by triggering the PI3K/AKT/mTOR cascade. The 8-loci ensemble stands as the optimal marker for MSI-H identification in CRC. ACVR2A, a central element within this group, deters CRC progression, while its suppression amplifies PI3K/AKT/mTOR signaling and angiogenesis under hypoxic stress.
Topics: Colorectal Neoplasms; Humans; Microsatellite Instability; Activin Receptors, Type II; Disease Progression; Animals; Cell Movement; Mice; Cell Line, Tumor; Cell Proliferation; Biomarkers, Tumor; Signal Transduction; Male; High-Throughput Nucleotide Sequencing; Female; Proto-Oncogene Proteins c-akt
PubMed: 38898042
DOI: 10.1038/s41598-024-62753-1 -
Equine Veterinary Journal Jun 2024Ancillary diagnostic methods to enhance the accuracy of viability assessment have not been established for use in clinical practice.
BACKGROUND
Ancillary diagnostic methods to enhance the accuracy of viability assessment have not been established for use in clinical practice.
OBJECTIVES
To assess intestinal microperfusion measured by Laser Doppler Flowmetry and Spectrophotometry (LDFS) in naturally occurring small intestinal strangulations of different origins and to compare this between viable and non-viable segments.
STUDY DESIGN
Prospective clinical trial.
METHODS
Forty horses undergoing colic surgery for naturally occurring small intestinal strangulations were included. Tissue oxygen saturation (tSO), haemoglobin (tHB) and blood flow (tBF) were determined by LDFS before and after release of the strangulation. Intestinal biopsies were taken in cases that underwent intestinal resection or intraoperative euthanasia and assessed using a semi-quantitative mucosal injury score (MIS). The LDFS measurements were compared between the different categories of strangulation causes and histopathological injury using parametric and non-parametric tests (p < 0.05).
RESULTS
Strangulations by pedunculated lipomas had lower tBF (13.9 ± 18 arbitrary units [AU]) than epiploic foramen entrapments (65.2 ± 61 AU; CI -1.697 to -0.2498; p = 0.005). Segments with MIS > 5 showed lower tBF during strangulation than segments with MIS < 4 (mean difference 61.1 AU; CI -1.119 to -0.07361; p = 0.03). This did not differ significantly following release of strangulation. Furthermore, there was a positive correlation between the inflammatory cell count and tBF during strangulation (r 0.34; CI 0.01 to 0.60; p = 0.04). The tSO and tHB did not differ between the different categories of lesions or injury.
MAIN LIMITATIONS
No biopsies could be taken from the intestinal segments that did not undergo resection. The duration of strangulation could not reliably be ascertained.
CONCLUSIONS
Blood flow measurements in naturally occurring strangulating lesions show a varying degree of ischaemia in different causes of strangulation. Intestinal blood flow measurements prior to release of the strangulation could potentially contribute to the identification of mucosal injury, yet a high individual variability and other contributing factors need to be considered.
PubMed: 38888520
DOI: 10.1111/evj.14118 -
CytoJournal 2024This study aims to assess the effectiveness of Short Stature Homeobox 2 (SHOX2) and RAS Association Domain Family 1 Isoform A (RASSF1A) gene methylation detection in...
OBJECTIVE
This study aims to assess the effectiveness of Short Stature Homeobox 2 (SHOX2) and RAS Association Domain Family 1 Isoform A (RASSF1A) gene methylation detection in residual liquid-based cytology (LBC) materials from Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration (EBUS-TBNA) and investigate the diagnostic accuracy of a comprehensive diagnostic approach.
MATERIAL AND METHODS
Between June 2022 and May 2023, a total of 110 cases that underwent EBUS-TBNA were enrolled in the study. SHOX2 and RASSF1A genes methylation detection using the residual cytological material, LBC, and cell block (CB) were conducted for each EBUS-TBNA case. The sensitivity and specificity of cytology, CB histopathology, SHOX2, and RASSF1A methylation in diagnosing EBUS-TBNA samples were determined based on follow-up data.
RESULTS
Among the 72 cases confirmed as pulmonary carcinomas, the methylation test yielded positive results in 24 adenocarcinoma cases, 10 squamous cell carcinoma cases, and 14 small cell carcinoma cases. The sensitivity of the comprehensive diagnosis (combining LBC, CB, and methylation detection) in distinguishing metastatic pulmonary epithelial malignancies in mediastinal and hilar lymph nodes or masses from benign lesions was higher (97.22%, 70/72) than that of morphological diagnosis alone (LBC and CB) (88.89%, 64/72; < 0.05).
CONCLUSION
SHOX2 and RASSF1A methylation detection demonstrates a high sensitivity and negative predictive value in the identification of pulmonary epithelial malignancies and holds promise as a valuable ancillary approach to enhance morphological diagnosis of EBUS-TBNA.
PubMed: 38887695
DOI: 10.25259/Cytojournal_114_2023 -
Health Psychology : Official Journal of... Jun 2024Adverse childhood experiences (ACEs) have been linked to adulthood chronic diseases, but there is little research examining the mechanisms underlying this association....
OBJECTIVES
Adverse childhood experiences (ACEs) have been linked to adulthood chronic diseases, but there is little research examining the mechanisms underlying this association. We tested pathways from ACEs to adult disease mediated via risk factors of depression, smoking, and body mass index.
METHOD
Prospective data from adults 18 to 74 years old from the Hispanic Community Health Study/Study of Latinos and Sociocultural Ancillary Study were used. Retrospectively reported ACEs and hypothesized mediators were measured at Visit 1 (2008-2011). Outcomes of disease prevalence were assessed at Visit 2, approximately 6 years later. The analytic sample includes 5,230 Hispanic/Latino participants with ACE data. Statistical mediation was examined using structural equation modeling on cardiometabolic and pulmonary disease prevalence and reported probit regression coefficients with 95% confidence intervals (CIs).
RESULTS
We found a significant association between ACEs and the prevalence of asthma/chronic obstructive pulmonary disorder (standardized β = .07, 95% CI [0.02, 0.12]). In the mediational model, the direct association was nonsignificant (β = .02, 95% CI [-0.04, 0.07]) but was mediated by depressive symptoms (β = .03, 95% CI [0.02, 0.04]). There were no associations between ACEs and the prevalence of diabetes and self-reported coronary heart disease or cerebrovascular disease. However, a small indirect effect was identified via depressive symptoms and coronary heart disease (β = .02, 95% CI [0.01, 0.03]).
CONCLUSION
In this diverse Hispanic/Latino sample, depressive symptoms were found to be a pathway linking ACEs to self-reported cardiopulmonary diseases, although the effects were of small magnitude. Future work should replicate pathways, confirm the magnitude of effects, and examine cultural moderators that may dampen expected associations. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
PubMed: 38884976
DOI: 10.1037/hea0001349 -
Heliyon Jun 2024In this study, we aimed to identify how Information Technology professionals make sense of digital transformation, in order to compare this perception with the...
In this study, we aimed to identify how Information Technology professionals make sense of digital transformation, in order to compare this perception with the scientific literature on the topic. To conduct the research, we adopted the Social Representation Theory. Thus, via an online tool, we applied the words evocation technique as well as an ancillary questionnaire comprising open and closed questions. The expressions collected were then semantically treated and categorized, being then analyzed vis-à-vis their frequency of evocation, relevance, connectedness, and cooccurrence. Then, we performed similarity and content analyses for the open answers received. In doing so, we detected dissonance between scientific production on the concept of digital transformation and the perception of Information Technology professionals on this construct, concluding that such professionals have a technocentric view of digital transformation, based mainly on its technological aspects, which can prevent digital transformation initiatives from fully achieving the desired objectives.
PubMed: 38882268
DOI: 10.1016/j.heliyon.2024.e31591 -
Fundamental & Clinical Pharmacology Jun 2024Mycophenolate mofetil (MMF) has been used to treat interstitial lung disease (ILD), but mycophenolate (MPA) pharmacokinetics was not reported for this use. This...
BACKGROUND
Mycophenolate mofetil (MMF) has been used to treat interstitial lung disease (ILD), but mycophenolate (MPA) pharmacokinetics was not reported for this use. This ancillary study of the EVER-ILD protocol aimed at describing the pharmacokinetic variability of MPA using population modelling in ILD.
METHODS
Concentrations of MPA were measured during an 8-h course for 27 ILD patients treated with 1000 mg MMF b.i.d. Absorption, distribution and elimination of MPA were described using population compartment models with first-order transfer and elimination rate constants, while accounting for both absorption peaks using gamma absorption models.
RESULTS
The pharmacokinetics of MPA was best described using a two-compartment model and two gamma absorption models, model performances of this model were still similar to those of a one gamma absorption model. This pharmacokinetics seemed to be notably influenced by body weight, renal function and inflammatory status. The distribubtion value area under the concentration curve between two administrations of MMF was AUC = 52.5 mg.h/L in median (interquartile range: 42.2-58.0 mg.h/L).
CONCLUSION
This is the first study reporting MPA pharmacokinetics in ILD. This pharmacokinetics appears to be similar to other indications and should be further investigated in future studies.
PubMed: 38880975
DOI: 10.1111/fcp.13021 -
Diagnostic Cytopathology Jun 2024Fine needle aspiration procedure is routinely used for cytological diagnosis of nodal or extra nodal lesions. Follicular dendritic cell sarcoma (FDCS) is a rare...
Fine needle aspiration procedure is routinely used for cytological diagnosis of nodal or extra nodal lesions. Follicular dendritic cell sarcoma (FDCS) is a rare mesenchymal neoplasm arising from follicular dendritic cells of lymphoid follicles at nodal and extranodal sites. Multimodal therapies have emerged for FDCS, necessitating its accurate pathologic diagnosis with additional ancillary testing for directing clinical management. By immunohistochemical analysis, FDCS is positive for the complement receptors CD21, CD23, and CD35. In addition, D2-40 is reported to be highly sensitive for FDCS with a strong membranous pattern of expression. In this study, we present the cytological diagnosis of a case of FDCS in retroperitoneal lymph nodes with an emphasis on a unique staining pattern of D2-40 which showed a strong nuclear pattern in tumor cells comparable to the membranous pattern of D2-40 on the control tissue and other surgical cases of FDCS in our comparative study.
PubMed: 38877799
DOI: 10.1002/dc.25371 -
Human Pathology Jun 2024Sweat gland neoplasms represent a challenging area of dermatopathology, as they are relatively uncommon and often histopathologically complex. Recent studies have...
Ancillary immunohistochemical and molecular testing in the classification of cutaneous sweat gland/duct neoplasms: A validation study with emphasis on histomorphologic correlation and pathological diagnosis.
Sweat gland neoplasms represent a challenging area of dermatopathology, as they are relatively uncommon and often histopathologically complex. Recent studies have uncovered distinct immunohistochemical and molecular profiles in several sweat gland neoplasms, including digital papillary adenocarcinoma (DPA), papillary eccrine adenoma/tubular apocrine adenoma (PEA/TAA), poroid family tumors (PFT)/porocarcinoma, and clear cell hidradenoma (CCH)/clear cell hidradenocarcinoma (CCHCa). To further evaluate the diagnostic utility of ancillary studies in various sweat gland neoplasms, we performed an independent validation study in a cohort of patients with acral and non-acral tumors (9 DPA, 8 PEA/TAA, 13 PFT, 5 porocarcinoma, 23 CCH, 7 CCHCa, 6 sweat gland carcinoma not otherwise specified). p63 immunohistochemistry (IHC) demonstrated a myoepithelial pattern in 8/8 DPA and 4 of 4 tested PEA/TAA cases, and showed a ductal pattern in all tested PFT/porocarcinoma and CCH/CCHCa cases (42/42). All PEA/TAA (8/8) cases were positive for BRAF V600E IHC. 5 of 12 tested PFT and 5/5 porocarcinoma cases showed either positive staining with NUT IHC or harbored YAP1::NUTM1 fusion gene by RNA sequencing. MAML2 fluorescence in situ hybridization (FISH) was positive in all CCH and CCHCa cases (23/23 and 7/7, respectively). Our results further support the usefulness of appropriate ancillary studies in precise classification of sweat gland tumors, which may be routinely applied in diagnostic pathology practice when morphologic evaluation is in doubt.
PubMed: 38876201
DOI: 10.1016/j.humpath.2024.06.006