Safety and efficacy of sodium zirconium cyclosilicate for the management of acute and chronic hyperkalemia in children with chronic kidney disease 4-5 and on dialysis.

BACKGROUND: Sodium zirconium cyclosilicate (SZC), an ion-exchange resin, is effective in the control of hyperkalemia in adults with chronic kidney disease (CKD); reports of use in children are limited. Prolonged therapy with SZC to relax dietary potassium restriction in CKD has not been examined. METHODS: We conducted a retrospective chart review of patients 6 months to 18 years of age with CKD stage 4-5 or on dialysis (5D) administered SZC for sustained hyperkalemia (potassium ≥ 5.5 mEq/L, three consecutive values). Patients received SZC (0.5-10 g per dose; age-based) either short-term (< 30 days) or long-term (> 30 days). RESULTS: Twenty patients with median age 10.8 (inter-quartile range 3.9, 13.4) years were treated with SZC. Short-term SZC, for 5 (3, 19) days, was associated with safe management of dialysis catheter insertions (n = 5) and access dysfunction (n = 4), and was useful during palliative care (n = 1). Serum potassium levels decreased from 6.7 (6.1, 6.9) to 4.4 (3.7, 5.2) mEq/L (P < 0.001). Long-term SZC for 5.3 (4.2, 10.1) months achieved decline in serum potassium from 6.1 (5.8, 6.4) to 4.8 (4.2, 5.4) mEq/L (P < 0.001). SZC use was associated with liberalization of diet (n = 6) and was useful in patients with poor adherence to dietary restriction (n = 3). Adverse events or edema were not observed; serum sodium and blood pressure remained stable. CONCLUSIONS: SZC was safe and effective for the management of acute and chronic hyperkalemia in children with CKD4-5/5D. Its use was associated with relaxation of dietary potassium restriction. Studies to examine its routine use to improve diet and nutritional status in children with CKD are required.

Gutted: constipation in children with chronic kidney disease and on dialysis.

Functional constipation is a common problem in otherwise healthy children. Children with chronic kidney disease (CKD) and on dialysis have additional disease-related risk factors including the uremic milieu, fluid and dietary restrictions, and decreased physical activity, as well as treatment-related risk factors such as dialysis therapy and polypharmacy that contribute to and compound the problem. Constipation causes significant distress for children and their caregivers. In children on peritoneal dialysis, severe constipation can impede catheter function and ultrafiltration. Accumulating evidence points to a possible bidirectional relationship between constipation and CKD, potentially mediated by gut dysbiosis with consequent increased generation of gut-derived uremic toxins and disruption of intestinal epithelium integrity leading to translocation of noxious luminal contents into the circulation inducing systemic inflammation. Effective management of constipation is required but there is little published data on the safety and effectiveness of treatments in adults or children with CKD. In this review, we discuss the diagnosis and epidemiology of functional constipation, provide an overview of its pathophysiology, summarize the therapeutic management, and reflect on the challenges in children with CKD.

Hypophosphatemia and Outcomes in ICU: A Systematic Review and Meta-Analysis.

PURPOSE: Hypophosphatemia is reported in up to 5% of hospitalized patients and ranges from 20% to 80% in critically ill patients. The consequences of hypophosphatemia for critically ill patients remain controversial. We evaluated the effect of hypophosphatemia on mortality and length of stay in intensive care unit (ICU) patients. METHODS: MEDLINE, EMBASE, Cochrane Library (Reviews and Trials), and PubMed were searched for articles in English. The primary outcome was mortality and secondary outcome was length of stay. The quality of evidence was graded using a modified Newcastle-Ottawa Scale. RESULTS: Our search yielded 828 articles and ultimately included 12 studies with 7626 participants in the analysis. Hypophosphatemia was associated with increased hospital length of stay (2.19 days [95% CI, 1.74-2.64]) and ICU length of stay (2.22 days [95% CI, 1.00-3.44]) but not mortality (risk ratio: 1.13 [95% CI, 0.98-1.31]; P = .09). CONCLUSIONS: Hypophosphatemia in ICU was associated with increased hospital and ICU length of stay but not all-cause mortality. Hypophosphatemia appears to be a marker of disease severity. Limited number of available studies and varied study designs did not allow for the ascertainment of the effect of severe hypophosphatemia on patient mortality.

Tumour-Infiltrating Inflammatory Cells in Early Breast Cancer: An Underrated Prognostic and Predictive Factor?

The role of tumour-infiltrating inflammatory cells (TIICs) in the disease progression of hormone-receptor-positive breast cancer (HR+ BC) is largely unclear since it is generally regarded as the least immunogenic BC subtype. This study investigated the prognostic significance of CD1a+ dendritic cells, CD20+ B cells, CD45RO+ memory T cells and CD4+ T-helper cells in HR+ BC. One hundred and forty-six patients were treated for early stage, distant-metastases-free HR+ BC in an accelerated partial breast irradiation (APBI) phase II trial. Immunohistochemistry was used to double-stain two adjoining sets of tissue microarrays from pre-RT (radiotherapy) tumour resection samples for CD1a/CD20 and CD45RO/CD4. Cell densities of CD1a+, CD20+, CD45RO+ and CD4+ TIICs in the stromal and intraepithelial compartment were registered semiautomatically. High densities of CD20+ and CD4+ TIICs were strongly associated with reduced disease-free survival (DFS), while high stromal CD45RO+ TIIC densities were indicators of subsequent successful treatment. An immunoscore based on CD20+ and CD45RO+ TIIC densities identified three different risk groups (p < 0.001). Thus, contrary to current assumptions, intratumoural immune cell composition might be an important prognostic indicator and a possible contributing factor in the outcome of HR+ BC and should be the subject of further research. Specifically, B-cell infiltration entailed an increased relapse rate and could play an important role in disease progression.

Optimizing Flux Capacity of Dead-end Filtration Membranes by Controlling Flow with Pulse Width Modulated Periodic Backflush.

Standard dead-end sample filtration is used to improve sample purity, but is limited as particle build-up fouls the filter, leading to reduced recovery. The fouling layer can be periodically cleared with backflush algorithms applied through a customized fluidic actuator using variable duty cycles, significantly improving particulate recovery percentage. We show a Pulse Width Modulation (PWM) process can periodically backflush the filter membrane to repeatedly interrupt cake formation and reintegrate the fouling layer into the sample, improving net permeate flux per unit volume of sample by partially restoring filter flux capacity. PWM flow for 2.19 um (targeted) and 7.32 um (untargeted) polystyrene microbeads produced 18-fold higher permeate concentration, higher recovery up to 68.5%, and an 8-fold enrichment increase, compared to a uniform flow. As the duty cycle approaches 50%, the recovery percentage monotonically increases after a critical threshold. Further, we developed and validated a mathematical model to determine that fast, small-volume backflush pulses near 50% duty cycle yield higher recovery by decreasing fouling associated with the cake layer. Optimized PWM flow was then used to purify custom particles for immune activation, achieving 3-fold higher recovery percentage and providing a new route to improve purification yields for diagnostic and cellular applications.

Accelerated Partial Breast Irradiation: Macrophage Polarisation Shift Classification Identifies High-Risk Tumours in Early Hormone Receptor-Positive Breast Cancer.

Studies have demonstrated correlations between accumulations of tumour-associated macrophages (TAMs), especially of M2-like phenotype, and increased mortality in advanced breast cancer. We investigated the prognostic potential of both main macrophage phenotypes in early hormone receptor-positive (HR+) breast cancer. The studied cohort of 136 patients participated in an institutional APBI phase II trial. Patient selection was characterized by HR+, small tumour size and no metastasis. Tissue microarrays from pre-RT resection samples were double stained for CD68/CD163 using immunohistochemistry. CD68+/CD163- cells were considered M1-like macrophages and CD68+/CD163+ was representative of M2-like macrophages. M1 and M2 macrophage densities were analysed semi-automatically in the stromal and intraepithelial tumour compartment. Low M1 and high M2 densities were strongly associated with decreased disease-free survival (DFS). Combined TAM phenotype densities were studied after defining a macrophage shift classification: M1-shifted (M1 high, M2 low) and non-shifted (M1 low, M2 low; M1 high, M2 high) tumours entailed a favourable outcome. In contrast, M2-shifted (M1 low, M2 high) TAM populations were associated with extremely reduced DFS. Thus, the full predictive potential of TAMs was revealed in a combined analysis of both phenotypes. The M2-shifted subgroup of tumours is classified as high-risk and probably not suitable for partial breast irradiation.