Apmis最新文献

Keratin 17 (K17) is frequently overexpressed, associated with poor prognosis in various cancers, and contributes to p27 degradation during cancer progression. Using immunohistochemistry, we evaluated K17 and p27 expression and assessed their biological behavior and prognostic significance in 326 colorectal cancers. High K17 expression was associated with poorly differentiated tumors, high pT classification, and lymph node metastases. Low p27 expression was associated with large tumors, high pT classification, lymphovascular invasion, and lymph node metastases. The overall survival of patients with high K17 expression was significantly worse than that of patients with low K17 expression [hazard ratio (HR) = 1.805, 95% confidence interval (CI) 1.169–2.787; p = 0.007]. Patients with low p27 expression showed significantly worse overall survival than those with high p27 expression (HR = 3.082, 95% CI 1.722–5.517; p < 0.001). When combining the results of K17 and p27 expression, the K17^highp27^low expression group showed the worst overall survival. On the contrary, the K17^high/lowp27^high group showed the best overall survival (p < 0.001). Therefore, K17^highp27^low expression is an independent poor prognostic factor in colorectal cancer. Thus, high K17 and low p27 expression correlate with aggressive clinicopathologic behavior and can be used as poor prognostic markers in colorectal cancer.

This review aimed to summarize the current literature on antibiotic distribution in orthopedically relevant tissues and settings where dynamic sampling methods have been used. PubMed and Embase databases were systematically searched. English-published studies between 2004 and 2024 involving systemic antibiotic administration in orthopedically relevant tissues and settings based on dynamic measurements were included. In total, 5385 titles were identified. After title and abstract screening, 97 eligible studies (43 different antibiotic drugs) were included. The studies covered both preclinical (42%) and clinical studies including healthy and infected tissues (21%) and prophylactic and steady-state situations (35%). Microdialysis emerged as the predominant sampling method in 98% of the studies. Most of the presented antibiotics (80%) were only assessed once or twice. Among the most extensively studied antibiotics were cefuroxime (18 studies), linezolid (9 studies) and vancomycin (9 studies). This review presents valuable insights into the microenvironmental distribution of antibiotics in orthopedically relevant target tissues and settings and seeks to provide a basis for improving dosing recommendations and treatment outcomes. However, it is important to acknowledge that our findings are limited to the specific drug, dosing regimens, administration method and target tissue, and are crucially linked to the selected PK/PD target.

The 2016 Amsterdam Placental Workshop Group Consensus Statement recommends sampling a block of the placenta close to the umbilical cord insertion site (UCIB) for histopathological evaluation. This piece of placenta at the umbilical cord insertion is presumed to give a better yield of inflammation (if present). We aimed to investigate the utility of the UCIB in the detection of maternal and/or fetal inflammatory responses (MIR and/or FIR), in comparison with the other sections of the placental parenchyma. This is a retrospective cross-sectional study including all placentas with histologic chorioamnionitis. The histopathological slides of placentas were reviewed as per Amsterdam consensus guidelines. Diagnostic performance of UCIB in identifying MIR and/or FIR, relative to the other placental sections, was assessed. UCIB revealed diagnostic sensitivity, specificity, and diagnostic accuracy of 79.2% (95% CI: 74.2–83.6%), 100.0% (95% CI: 95.6–100.0%), and 83.6% (95% CI: 79.5–87.2%), respectively, in the detection of FIR, while showing a low sensitivity of 52.6% (95% CI: 47.5–57.6%) in detecting MIR. In 59 (24.6%) cases, FIR was not seen in the corresponding placental parenchymal sections but was detected in the UCIBs. This study is the first study to confirm that a section from the UCIB is essential for the detection of FIR, which affirms the Amsterdam consensus sampling recommendations.

Antibodies and avidity maturation contribute to long-lasting immunity, and previous COVID-19 seems to enhance the immune response after vaccination. The aim of this study was to compare the immune response after vaccination between COVID-19 convalescents and naïve patients. Blood samples from COVID-19 convalescents and naïve patients, taken 1, 3 and 6 months after the second dose of vaccine (mRNA-vaccine BNT162b2), were analysed for anti-spike IgG and avidity. Questionnaires concerning side effects were used. Thirty-one patients in the COVID-19 cohort and 30 patients in the naïve cohort were included. High levels of anti-spike IgG and avidity index were seen. Anti-spike IgG were significantly higher in the COVID-19 cohort and declining (median 1250, 566, 282 RU/ml vs 565, 187, 65 RU/ml). Avidity did not change over time (median at 6 months 78% vs 65%). The most common side effects were pain at the injection site, malaise and headache. In conclusion, high levels of anti-spike IgG after vaccination were seen and most patients developed high-avidity antibodies, although antibody levels and avidity were higher in the COVID-19 cohort. Over time, the levels of anti-spike IgG declined, yet avidity remained high. Side effects did not differ between groups and were of short duration.

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.