Measurement of innate immune response biomarkers in peritoneal dialysis effluent using a rapid diagnostic point-of-care device as a diagnostic indicator of peritonitis

Peritonitis is the commonest complication of peritoneal dialysis and a major reason for treatment failure. Current diagnosis is based on clinical symptoms, cloudy effluent and a dialysate white cell count (over 100 cells/μl). A rapid point-of-care diagnostic test would accelerate diagnosis and potentially improve outcomes from infection. Here, in a clinical audit project, we used PERiPLEX®, a point-of-care device which detects when levels of matrix metalloproteinase-8 and interleukin-6 are elevated above a threshold within minutes in dialysis effluent, to assess whether it could confirm or exclude peritonitis in 107 patients undergoing peritoneal dialysis. Mean patient age was 64.6 years with a median duration of peritoneal dialysis of 3.5 months (interquartile range 6.4 – 31.5 months). Presence of peritonitis was confirmed by clinical criteria. There were 49 positive tests of which 41 patients had peritonitis, three had other causes of intra-peritoneal inflammation, three had severe urosepsis and two patients required no treatment. Fifty eight tests were negative with one patient having a false negative result. The positive predictive value of the test was 83.7% (95% confidence interval 72.8 – 90.8) and the negative predictive value was 98.3% (89.1 – 99.8). Sensitivity and specificity were 97.6% (87.4 – 99.9) and 87.7% (77.2 – 94.5) respectively. Thus, PERiPLEX® could be used as a rapid point-of-care test that can aid the diagnosis or exclusion of peritonitis with a high negative predictive value

Oncogenic Properties of Apoptotic Tumor Cells in Aggressive B Cell Lymphoma

BACKGROUND: Cells undergoing apoptosis are known to modulate their tissue microenvironments. By acting on phagocytes, notably macrophages, apoptotic cells inhibit immunological and inflammatory responses and promote trophic signaling pathways. Paradoxically, because of their potential to cause death of tumor cells and thereby militate against malignant disease progression, both apoptosis and tumor-associated macrophages (TAMs) are often associated with poor prognosis in cancer. We hypothesized that, in progression of malignant disease, constitutive loss of a fraction of the tumor cell population through apoptosis could yield tumor-promoting effects. RESULTS: Here, we demonstrate that apoptotic tumor cells promote coordinated tumor growth, angiogenesis, and accumulation of TAMs in aggressive B cell lymphomas. Through unbiased "in situ transcriptomics" analysis-gene expression profiling of laser-captured TAMs to establish their activation signature in situ-we show that these cells are activated to signal via multiple tumor-promoting reparatory, trophic, angiogenic, tissue remodeling, and anti-inflammatory pathways. Our results also suggest that apoptotic lymphoma cells help drive this signature. Furthermore, we demonstrate that, upon induction of apoptosis, lymphoma cells not only activate expression of the tumor-promoting matrix metalloproteinases MMP2 and MMP12 in macrophages but also express and process these MMPs directly. Finally, using a model of malignant melanoma, we show that the oncogenic potential of apoptotic tumor cells extends beyond lymphoma. CONCLUSIONS: In addition to its profound tumor-suppressive role, apoptosis can potentiate cancer progression. These results have important implications for understanding the fundamental biology of cell death, its roles in malignant disease, and the broader consequences of apoptosis-inducing anti-cancer therapy

Clinical and Cytokine Predictors of Outcomes in Peritoneal Dialysis

Background Changes in the structure and function of the peritoneal membrane limit the duration of PD. Rarely (and unpredictably) these changes progress to severe fibrosis and bowel encapsulation (encapsulating peritoneal sclerosis, EPS) with substantial morbidity and mortality. Methods PD fluid and serum samples from 50 patients were added to 100 previously analysed samples (Dr S Ahmad). CCL18, IL-6, MCP-1 and angiogenin were measured by ELISA. CCL15 was measured for the first time in 125 serum and dialysate samples. Fifty one year follow up samples were analysed. Serum cytokines were measured in patients with and without EPS. Peritoneal mesothelial cells were cultured and media cytokine levels measured. CCL15 stimulation of cytokine production was investigated. Protein transfer across the peritoneal membrane by size was investigated. CT scans from 20 pre-EPS PD patients were scored and compared with scans of non-EPS patients. Results Levels of CCL18, MCP-1, CCL15, angiogenin and IL-6 in dialysate correlate with clinically important measures such as glucose exposure and D/P creatinine. Mesothelial cells in culture produce MCP-1, IL-6, angiogenin and CCL18. High dialysate levels of MCP-1, IL-6 and CCL15 are found in patients who subsequently developed EPS. High levels of CCL18 are also seen in haemodialysis patients with EPS. CT screening of PD patients used alone does not predict future EPS; in combination with abdominal symptoms CT scans may be of use. Conclusions There is local peritoneal production of chemokines such as MCP-1, CCL18, IL-6 and angiogenin, and the correlation of levels of these cytokines with clinically relevant parameters suggests they may be involved in the pathogenesis of long term changes in the peritoneum. At present neither clinical nor cytokine levels can reliably be used to predict future EPS. CT scanning may be helpful in patients at risk of EPS who develop new abdominal symptoms

Neutralising antibodies after COVID-19 vaccination in UK haemodialysis patients.

No abstract available