Apmis最新文献

Large B-cell lymphomas (LBLs) comprise a genetically heterogeneous group of clinically aggressive non-Hodgkin lymphomas, frequently exhibiting overlapping features with diffuse large B-cell lymphoma and Burkitt's lymphoma. We report a case of a 24-year-old, previously healthy male with a classical clinical presentation of acute appendicitis. The pathologic examination discovered a large B-cell lymphoma with MYC and BCL6 rearrangements in the excised appendix. The patient was assigned Stage IEA, IPI = 0 and received chemotherapy. This case depicts a very uncommon occurrence of fully localized LBL in a patient of an unusually young age and clinical presentation for this type of lymphoma.

Accumulating research has revealed that src-homology domain 2-containing protein tyrosine phosphatase-2 (SHP2), an oncogenic protein tyrosine phosphatase, is associated with liver fibrosis. Currently, it is still unclear whether SHP2 affects liver fibrosis by influencing the apoptosis of hepatic stellate cells (HSC). In present study, we investigate effects of SHP2 expression changes on liver fibrosis, with special emphasis on the apoptosis of HSC. Using adenovirus vector, wild-type SHP2 gene and short hairpin RNA targeting SHP2 were introduced into rats with liver fibrosis and LX-2 cells in vitro. The expressions of type I and III collagen, pathological and functional changes, collagen deposition in rat liver and apoptosis of LX-2 cells were detected by immunohistochemical and HE staining, automated biochemical analyzer, Masson trichrome staining, and TUNEL. This study showed that overexpression of SHP2 exacerbated dysfunction, inflammatory damage, collagen deposition and increased expression of type I and III collagen in rat liver reduced apoptosis of LX-2 cells. On the contrary, low expression of SHP2 alleviated the aforementioned detection indicators of rats and promoted apoptosis of LX-2 cells. In conclusion, the downregulation of SHP2 expression alleviates liver fibrosis by inducing the apoptosis of HSC, while overexpressed SHP2 exacerbates liver fibrosis by inhibiting the apoptosis of HSC.

The study evaluated the accuracy and clinical impact of rapid diagnostics (RD) with or without antibiotic decision support (ADS) for hospitalized patients with urinary tract infections. A two-centre prospective intervention was conducted with 230 patients divided into three groups: RD-only (n = 59), RD plus ADS (n = 56) and a control group (n = 115). Mean laboratory turnaround time for RD was 10 h and 50 min. Of 115 microorganisms, 108 were correctly identified. The error rate for rapid susceptibility determination was 0.85%. Total antibiotic consumption, measured in defined daily doses (DDD), was lower in the intervention groups compared to the control group (ADS: 10.3 DDD, p = 0.01; RD: 10.9 DDD, p = 0.06; control: 13.0 DDD). No significant differences were observed in the use of broad-spectrum antibiotics (p = 0.816). Adherence to antibiotic guidelines was significantly better in the ADS group compared to the control group (p = 0.015) (RD vs control; p = 0.261). The ADS group also received fewer doses of ineffective antibiotics (ADS: 1.8 doses, p = 0.012; RD: 2.4 doses, p = 0.195; control: 3.4 doses). Length of hospital and ICU stays or 30-day readmission rates did not differ across groups. No in-hospital mortality was observed in any group.

Like their natural counterparts, chimeric antigen receptor-engineered cells are prone to suppression by inhibitory signals, such as PD-L1, expressed by tumors or suppressor cells in the tumor microenvironment. Consequently, they become impaired, resulting in immune cell exhaustion, tumor progression, and resistance to other therapies. In this study, we developed an anti-PD-L1-CAR NK cell with efficient activity and a notable PD-L1-specific response toward tumor cell lines. The degranulation assay demonstrated that CD107a frequencies between the PD-L1^med and PD-L1^high groups and between Herceptin-treated and non-treated groups were not statistically different. Further investigation into NK cell characterization, considering different markers such as CD57, KIR2D, and CD25, revealed that the majority of the population are activated expanding NK cells. At the same time, immune checkpoint inhibitors, including PD-1, PD-L1, and LAG-3, showed increased levels following activation and expansion. Regarding the efficient functional activity of PD-L1-CAR NK cells and the instinctive receptor balance-based response of NK cells, this observation could point to the inhibition of NK cell overactivation or even higher cytotoxicity and cytokine production rather than exhaustion, especially in the case of healthy NK cells. These findings can contribute to a better understanding of the potential and challenges of using primary NK cells for CAR-NK cell therapy.

Clonal hematopoiesis is highly prevalent in elderly patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN), and around 20% of BPDCN patients have an associated myeloid malignancy. We present a patient with localized BPDCN and concomitant myelodysplastic syndrome (MDS), previously followed for several years due to clonal cytopenia of unknown significance. Compared targeted next-generation sequencing (NGS) of the skin tumor and sequential bone marrow samples showed shared variants in ASXL1 and TET2 with a de novo NRAS variant in both BPDCN and MDS compared to preceding bone marrow samples. These findings illustrate a shared clonal origin of BPDCN and MDS resulting from progressive clonal hematopoiesis.

Accurate detection of Helicobacter pylori and its antimicrobial resistance is essential for eradication of the infections. The aim of this study was to compare five different CE-IVD marked assays in detection of H. pylori from 268 clinical stool samples. Samples were considered positive for H. pylori when at least three of the five tests were positive. Amplified IDEIA Hp StAR (Oxoid) and Premier Platinum HpSA PLUS (Meridian Bioscience Inc.) assays showed sensitivity of 100% [95% CI (confidence interval): 87-100] and LIAISON® Meridian H. pylori SA (DiaSorin) of 83.3% (95% CI: 66-93). Specificities of the assays were 94.5% (95% CI: 91-97), 95.4%; (95% CI: 92-97), and 97.1% (95% CI: 94-99) respectively. Amplidiag® H. pylori + ClariR (Mobidiag) assay showed 93.3% (95% CI: 78-99) and Allplex™ H. pylori & ClariR Assay (Seegene Inc.) 36.7% (95% CI: 22-55) sensitivity, while specificity of both was 97.9% (95% CI: 95-99). The Amplidiag® and Allplex™ assays concordantly detected clarithromycin resistance in positive for H. pylori samples. The Amplidiag® assay showed the highest accuracy, namely 97.4% (95% CI: 95-99). These data provide helpful information for planning laboratory diagnostics of H. pylori and detection of clarithromycin resistance from stool samples.

Phyllodes tumors (PTs) are rare breast tumors showing overlapping features with fibroadenomas (FAs). Diagnosis on small biopsies is challenging. New diagnostic markers are needed. Here we evaluated immunohistochemical staining of histone 3 trimethyl-lysine-27 (H3K27me3) as a diagnostic and prognostic marker in a series of PTs. Surgically removed PTs at our institution (September 1990 and July 2022) and control FAs. Tissue micro-arrays (4 cores, 2 mm Ø) stained with H3K27me3, and scored with QuPath-derived H-score. Fisher exact test, Mann-Whitney U-test and chi-squared test used for group comparison. ROC analysis applied to define cutoffs. Cox proportional hazards models were used for assessing disease-free survival (DFS), overall survival (OS), and disease-specific survival (DSS) in PTs. We included 81 patients with PTs and 44 patients with FAs. QuPath-derived H-scores of stromal H3K27me3 were statically significantly lower in PTs than in FAs (p < 0.001). We identified exploratory cutoffs to discriminate FAs from benign and malignant PTs (AUC = 0.78 and 0.73, respectively). No associations between DFS, OS, or DSS and H3K27me3 expression were found. H3K27me3 expression differs between FAs and PTs, indicating potential as diagnostic marker, but it is not predictive for DFS, OS or DSS in PTs. Further validation is needed.

Orthopaedic implant material can get infected via haematogenous spread from a distant source at any point after implantation. The sources of haematogenous orthopaedic implant infections have been studied only for prosthetic joints. The most common source of infection has varied, but it can be, for example from the skin and soft tissues, cardiovascular system and dental infections. The risk for developing a periprosthetic joint infection (PJI) during bacteraemia is dependent on the pathogen: it is highest for Staphylococcus aureus and beta-haemolytic streptococci, but low for gram-negative bacteria. The risk for developing a (PJI) during Staphylococcus aureus bacteraemia (SAB) has varied between 12 and 41%; the risk for developing an infection in any orthopaedic implant in the extremities during SAB is probably almost the same as for prosthetic joints, but data are very limited. The risk of developing an infection in spinal implants during bacteraemia is not known, as it has not been studied. Especially in the case of SAB, infected orthopaedic implants are usually symptomatic, so asymptomatic implants do not routinely require further diagnostic work-up, such as synovial fluid aspiration.

This research comprehensively investigates the epidemiological features and pathogen profile of acute respiratory infections (ARI) in Shihezi City, Xinjiang. A pivotal aspect of this study is the construction of a Bayes discriminant function for principal pathogen infections. This innovative methodology aims to furnish a robust scientific basis for the prevention and clinical management of ARI, potentially guiding more effective strategies in both public health and clinical settings. We compiled and examined data from January 2020 to June 2023, pertaining to patients admitted with acute respiratory infections at the First Affiliated Hospital of Shihezi University. This investigation focused on discerning patterns in epidemiology and pathogen etiology. Among 2110 cases of acute respiratory infections (ARI), 1736 underwent pathogenetic testing. Of these, 595 cases tested positive for at least one pathogen, marking a positivity rate of 34.27%. Viral detections, at a rate of 27.47%, were notably higher than bacterial detections, which stood at 6.51%. The most prevalent viruses identified were Human respiratory syncytial virus (hRSV), Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), and Human adenovirus (HAdV), while the dominant bacterial pathogens included Klebsiella pneumoniae, Haemophilus influenzae, and Staphylococcus aureus. Co-infections were observed in 76 cases, accounting for 12.77% of positive diagnoses, predominantly involving hRSV in conjunction with other pathogens. In cases of acute bronchiolitis, hRSV was the most frequent pathogen, contributing to 23.10% of such cases. Similarly, in severe pneumonia cases, SARS-CoV-2 was predominant, accounting for 25.4% of these infections. The group with bacterial positivity exhibited elevated levels of C-reactive protein (CRP, 19.17 mg/L) and neutrophilic granulocyte percentage (NE%, 54.7%). The Bayes discriminant function demonstrated an initial validation accuracy of 74.9% and a cross-validation accuracy of 63.7%. The study underscores that hRSV, SARS-CoV-2, and HAdV are the primary pathogens in acute respiratory infections in the Shihezi region. Pathogen susceptibility exhibits variation across different age groups, with a higher pathogen detection rate in children compared to adults. The Bayes discriminant function shows significant promise in the classification and diagnosis of major pathogenic infections.

Gynecologic cancers remain a frequent and deadly diagnosis. Historically, treatment has focused on a "one size fits all" approach, but there is an urgent need for more personal medicine. Hence, to enhance personal medicine, new biomarkers are needed. Samples from the Danish Cancer Biobank (DCB) may be well-suited for biomarker studies, as the biobank contains samples from more than 100.000 cancer patients, and the samples are annotated with pre-analytical variables. The aim of this study was to investigate if the recorded pre-analytical variables indicate the gynecologic tissue in DCB are suited for biomarker studies. Data on processing time, transport time, and registration- and verification status were extracted from all patients with a gynecologic tissue sample collected between 2020 and 2022 in DCB. The mean processing time across centers was found to be 1.03 h (SD = 0.71), and the mean transport time was found to be 0.32 h (SD = 0.70). In total, 69% of the tissue samples were pathologically examined, and 91.5% of the pathologically examined samples were found to be concordant with the patient's final diagnosis. While differences were observed, 98% of the samples were processed within 3 h, indicating the majority of gynecologic tissue samples in DCB are of high quality and optimal for biomarker studies.