Urgent-Start Peritoneal Dialysis: Brazilian Experience.

INTRODUCTION: Unplanned peritoneal dialysis (PD) is an important option for chronic kidney disease (CKD) patients requiring kidney replacement therapy urgently as it offers the convenience of home-based therapy. The objective of this study was to assess the Brazilian urgent-start PD program in three different dialysis centers where there is shortage of hemodialysis (HD) beds. METHODS: This prospective, multicentric cohort study included incident patients with stage 5 CKD and no permanent vascular access established who started urgent PD between July 2014 and July 2020 in three different hospitals. Urgent-start PD was defined as initiation of treatment up to 72 h after catheter placement. Patients were followed up from catheter insertion and assessed according to mechanical and infectious complications related to PD, patients, and technique survival. RESULTS: Over 6 years, 370 patients were included in all three study centers. Mean patient age was 57.8 ± 16.32 years. Diabetic kidney disease was the main underlying condition (35.1%) and uremia was the main cause for dialysis indication (81.1%). Concerning complications related to PD, 24.3% had mechanical complications, 27.3% had peritonitis, 28.01% had technique failure, and 17.8% died. On logistic regression, hospitalization (p = 0.003) and exit site infection (p = 0.002) were identified as predictors of peritonitis, while mechanical complications (p = 0.004) and peritonitis (p < 0.001) were identified as predictors of technique failure and switching to HD. Age (p < 0.001), hospitalization (p = 0.012), and bacteremia (p = 0.021) were observed to predict death. The number of patients on PD increased at least 140% in all three participating centers. CONCLUSION: PD is a feasible option for patients starting dialysis in an unplanned manner and may be a useful tool for reducing shortage of HD beds.

Combination of vitamin D and probiotics inhibits chemically induced colorectal carcinogenesis in Wistar rats.

The modulation of inflammatory elements, cell differentiation and proliferation by vitamin D and the role of probiotics in the intestinal microbiota and immunogenic response have sparked interest in the application of both in chemotherapeutics and chemoprevention of colorectal tumors. AIMS: The present study aimed to investigate the effects of isolated and/or combined treatment of vitamin D3 and probiotics on colorectal carcinogenesis. MAIN METHODS: Pre-neoplastic lesions were induced with 1,2-dimethylhydrazine in the colon of Wistar rats, which were treated with probiotics and/or vitamin D in three different approaches (simultaneous, pre-, and post-treatment). We investigated the frequency of aberrant crypt foci (ACF) and aberrant crypt (AC) in the distal colon, fecal microbiome composition, gene and protein expression through immunohistochemical and RT-PCR assays, and general toxicity through water consumption and weight gain monitoring. KEY FINDINGS: Results confirm the systemic safety of treatments, and show a protective effect of vitamin D and probiotics in all approaches studied, as well as in combined treatments, with predominance of different bacterial phyla compared to controls. Treated groups show different levels of Nrf2, GST, COX2, iNOS, ß-catenin and PCNA expression. SIGNIFICANCE: These experimental conditions explore the combination of vitamin D and probiotics supplementation at low doses over pathways involved in distinct stages of colorectal carcinogenesis, with results supporting its application in prevention and long-term strategies.

A synthetic resveratrol-curcumin hybrid derivative exhibits chemopreventive effects on colon pre-neoplastic lesions by targeting Wnt/ß-catenin signaling, anti-inflammatory and antioxidant pathways.

ABSTRACT: Based on the effectiveness of resveratrol and curcumin in carcinogenesis, (E)-3-(4-hydroxy-3-methoxyphenyl)-N'-((E)-4-methoxybenzylidene) acrylohydrazide (PQM-162), curcumin-resveratrol hybrid derivative, was designed by molecular hybridization using a hydrazone functionality as a spacer moiety between pharmacophoric fragments inspired by the parent compounds. OBJECTIVES: The present study aimed to evaluate the chemopreventive effects of the hybrid against pre-neoplastic lesions induced in the colon of rodents. METHODS: The doses were determined based on the reduction in DNA damage induced by doxorubicin [15 mg/kg body weight (b.w.)] in peripheral blood of Swiss mice. Doses of 8, 16, 32, and 64 mg/kg b.w. were antimutagenic. For the evaluation of pre-neoplastic lesions in the colon, Wistar rats were treated with PQM-162 at doses of 0.5, 1, and 2 mg/kg b.w. for 6 weeks using three approaches: simultaneous treatment, pre-treatment, and post-treatment. Pre-neoplastic lesions were induced with 1,2 dimethylhydrazine (160 mg/kg b.w.). KEY FINDINGS: PQM-162 reduced the formation of aberrant crypt foci in the simultaneous treatment and post-treatment. TNF-α and COX-2 mRNA levels decreased, while Nrf2 mRNA levels increased. PQM-162 also reduced the expression of COX-2, PCNA, and ß-catenin protein markers and increased Nrf2 expression. CONCLUSION: Our findings suggest a chemopreventive potential of PQM-162 in colorectal carcinogenesis, which acts on anti-inflammatory, antioxidant, and cell proliferation pathways.