Evaluation of fine-needle core biopsy specimens for pancreatic ductal adenocarcinoma: Diagnostic utility and helpful histological features.

AIMS: With the advent of new biopsy devices, fine-needle core biopsy specimens can be obtained from pancreas masses. This study aimed to report the histological spectrum of intrapancreatic adenocarcinoma on fine-needle core biopsy and the accuracy of sampling. METHODS AND RESULTS: We identified 423 SharkCore™ fine-needle core biopsies taken from patients with a high clinical concern for pancreatic adenocarcinoma. For each, we recorded patient age and sex, percentage of diagnostic tissue in each sample and tumour site, size and histological findings. The cases came from 392 patients (193 men, 199 women; mean age 69 years). Median diagnostic tissue amount in the samples was 30%. Common histological findings included desmoplasia (36%), single atypical cells (44%), haphazard glandular growth pattern (68%), nuclear pleomorphism > 4:1 (39%), incomplete gland lumens (18%) and detached atypical epithelial strips (37%). Additional levels were ordered on 143 cases. Final clinical diagnoses associated with the 423 cases were adenocarcinoma (n = 343), pancreatitis (n = 22), intraductal neoplasm or other benign/low-grade process (n = 16) and unknown (n = 42, patients lost to follow-up). Of the adenocarcinoma cases, the diagnosis was established by the evaluated fine-needle core biopsy sample alone in 178, by fine-needle aspiration biopsy alone in 30, by both concurrently in 89 and by subsequent biopsy or resection in 37 cases. Among 68 cases called suspicious on fine-needle core biopsy, 78% ultimately represented adenocarcinoma. CONCLUSIONS: Fine-needle core biopsy allows for histological diagnosis of pancreatic adenocarcinoma, using known histological parameters. Common findings include single atypical cells, desmoplasia, haphazard gland growth and nuclear pleomorphism. Cases interpreted as suspicious often represent malignancy.

The Impact of Hemolysis-Index Thresholds on Plasma and Serum Potassium Measurements.

BACKGROUND: Modern clinical laboratory analyzers measure a hemolysis index (H-index) because test results can be inaccurate when intracellular contents from erythrocytes leak into serum or plasma. In 2020, Roche Diagnostics decreased the H-index from 90/100 to 20 for potassium, recommending that laboratories avoid using specimens with an H-index >20; however, there are a limited number of studies investigating the impact of this recommendation on patient testing. METHODS: Out of 113 916 serum or plasma potassium tests performed within a 6-month interval, 72 patients with potentially hemolyzed potassium specimens (H-index >20) and a second non-hemolyzed specimen (H-index ≤20) within 2 h were identified. The clinical impact of decreasing the H-index and the utility of applying a corrective formula for adjusting potassium results were evaluated. RESULTS: The majority of initial test results either had small differences between original and corrected results that would not have affected clinical management or H-indices above the threshold previously recommended by Roche. We estimated the second sample was reported an average of 3 h 23 min after the initial sample was collected, with 95% CI [2 h 37 min to 4 h 8 min], and the median time delay was 2 h 44 min. CONCLUSIONS: Our analysis does not show a clear benefit from avoiding the use of potassium specimens above an H-index threshold of 20. Our findings suggest these practices may be detrimental in terms of patient safety due to increased turnaround time for a critical analyte.

New horizons in understanding the experience of Chinese people living with dementia: a positive psychology approach.

As the global average age increases, the incidence of dementia is also rising. Given improvements in diagnosis and life expectancies, people now live longer with dementia. Thus, the wellbeing and quality of life among people living with dementia are increasingly important areas for research. Research with Western populations has recently begun to apply positive psychology concepts to understand wellbeing in people with dementia. Positive psychology focuses on positive emotions and traits that allow individuals to flourish and thrive-it highlights the possibility of positive subjective experiences in the face of loss and functional decline, and contrasts the traditional deficit-focused perception of dementia. Despite being a major driver in the global growth of dementia prevalence, there is a dearth of research using such positive concepts to understand people with dementia in non-Western communities. This review contains discussion of research on positive constructs in Chinese older adults, and parallels between traditional Chinese cultural values and positive psychology. On this basis, we propose the applicability of a positive psychology framework to Chinese people with dementia, and that 'harmony' is an important culturally specific concept to consider in this area of research. A positive psychology approach acknowledges that strengths and positive experiences can endure after dementia diagnosis. This not only adds to the under-researched area of lived experience of dementia in Chinese people, but highlights areas that could be the focus of interventions or measured as outcomes. By improving understanding, this approach also has potential to reduce carer burden and stigma around dementia.

Hypoxia-inducible factor 1 alpha is regulated by RBM38, a RNA-binding protein and a p53 family target, via mRNA translation.

Hypoxia-inducible factor 1 (HIF1), a heterodimeric transcription factor, consists of HIF1α and HIF1ß and is necessary for cell growth and survival under a hypoxic condition. Thus, the level and activity of HIF1α needs to be tightly controlled. Indeed, HIF1α protein stability is controlled by prolyl hydroxylase and von Hippel-Lindau-mediated proteosomal degradation. However, it remains unclear whether HIF1α expression is controlled by other pathways. Here, we showed that RNA-binding protein RBM38, a target of the p53 family, regulates HIF1α expression via mRNA translation. Specifically, we showed that under a hypoxic condition, ectopic expression of RBM38 decreased, whereas knockdown of RBM38 increased, the level of HIF1α protein. We also showed that the rate of de novo HIF1α protein synthesis was increased by knockdown of RBM38. Additionally, we showed that RBM38 directly bound to HIF1α 5' and 3'UTRs. Consistently, we showed that the rate of mRNA translation for a heterologous reporter that carries HIF1α 5'and/or 3'UTRs was increased upon knockdown of RBM38. Furthermore, we showed that knockdown of RBM38 increased, whereas ectopic expression of RBM38 decreased, the binding of eIF4E to HIF1α mRNA. Together, our data suggest that RBM38 is a novel translational regulator of HIF1α under a hypoxic condition.

RNPC1, an RNA-binding protein and a p53 target, regulates macrophage inhibitory cytokine-1 (MIC-1) expression through mRNA stability.

Macrophage inhibitory cytokine-1 (MIC-1), a secreted cytokine, is a direct target of p53 and known to play a role in cell proliferation, apoptosis, cell metastasis, and angiogenesis through autocrine and paracrine signaling. Previous studies have shown that serum levels of MIC-1 closely parallel cancer progression and are being explored as a diagnostic tool. MIC-1 has also shown potential as a therapeutic agent as it has exhibited several anti-carcinogenic activities. Thus, MIC-1 displays two opposing effects: tumor suppression versus promotion. However, it remains unclear whether MIC-1 is regulated by a mechanism other than transcription and how MIC-1 exerts its tumor suppression. In this study, we show that overexpression of RNA-binding protein RNPC1 can increase, whereas knockdown or knock-out of RNPC1 decreases, MIC-1 transcript and protein levels. Additionally, we demonstrate that RNPC1 can bind to MIC-1 mRNA via an AU-rich element within MIC-1 3'-UTR and then enhances MIC-1 mRNA stability. Finally, to explore the functional significance of MIC-1, we showed that knockdown of MIC-1 can decrease RNPC1-induced cell growth suppression. Altogether, we uncover a novel mechanism by which MIC-1 can be regulated through RNPC1 via mRNA stability.