The role of nutritional vitamin D in CKD-MBD in children and adults with CKD, on dialysis and after kidney transplantation - a European consensus statement.

Vitamin D deficiency is common in patients with chronic kidney disease (CKD) and associates with poor outcomes. Current clinical practice guidelines recommend supplementation with nutritional vitamin D as for the general population. However, recent large-scale, clinical trials in the general population failed to demonstrate a benefit of vitamin D supplementation on skeletal or non-skeletal outcomes, fueling a debate on the rationale for screening for and correcting vitamin D deficiency, both in non-CKD and CKD populations.

Survey of legislative frameworks and national recommendations governing paediatric maintenance haemodialysis in Europe.

Background: The application of international recommendations for paediatric maintenance haemodialysis (HD) could be strengthened by national laws or written recommendations. Our aim was therefore to describe the national rules governing paediatric maintenance HD in European countries.

Methods: A national representative, approved by the president of each paediatric nephrology society, was contacted in all 42 European countries to complete two online questionnaires.

Mineral Stress Drives Loss of Heterochromatin: An Early Harbinger of Vascular Inflammaging and Calcification.

Background: Vascular calcification is a detrimental aging pathology markedly accelerated in patients with chronic kidney disease. Prelamin A is a biomarker of vascular smooth muscle cell aging that accelerates calcification however the mechanisms remain undefined.

Methods: Vascular smooth muscle cells were transduced with prelamin A using an adenoviral vector and epigenetic modifications were monitored using immunofluorescence and targeted polymerase chain reaction array.

Distinct molecular and clinical features of specific variants of KRAS codon 12 in pancreatic adenocarcinoma.

PURPOSE Oncogenic mutations in KRAS have been identified in > 85% of pancreatic ductal adenocarcinoma (PDAC) cases. G12D, G12V, and G12R are the most frequent variants. Using large clinical and genomic databases, this study characterizes prognostic and molecular differences between KRAS variants, focusing on KRAS G12D and G12R.

Directed evolution of an orthogonal transcription engine for programmable gene expression in eukaryotes.

T7 RNA polymerase (RNAP) has enabled orthogonal control of gene expression and recombinant protein production across diverse prokaryotic host chassis organisms for decades. However, the absence of 5' methyl guanosine caps on T7 RNAP-derived transcripts has severely limited its utility and widespread adoption in eukaryotic systems. To address this shortcoming, we evolved a fusion enzyme combining T7 RNAP with the single subunit capping enzyme from African swine fever virus using .

Economic hardships during COVID-19 and maternal mental health: Combining samples with low incomes across three cities.

The COVID-19 pandemic increased maternal depression and anxiety, imperiling both mothers' own wellbeing and that of their children. To date, however, little is known about the extent to which these increases are attributable to economic hardships commonly experienced during the pandemic: income loss, job loss, and loss of health insurance. Few studies have examined the individual impacts of these hardships, and none have lasted beyond the first year of the pandemic.

Clinical Practice Recommendations on Kidney Management in Methylmalonic Acidemia: an Expert Consensus Statement From ERKNet and MetabERN.

Methylmalonic acidemias (MMAs) are rare inherited metabolic diseases with multiorgan involvement. Chronic kidney disease (CKD) is a common complication, leading to kidney failure, dialysis, and kidney transplantation (KT). The objective of these guidelines was to develop clinical practice recommendations focusing on specific aspects of the kidney management of this disease.

SWOG S1815: A Phase III Randomized Trial of Gemcitabine, Cisplatin, and Nab-Paclitaxel Versus Gemcitabine and Cisplatin in Newly Diagnosed, Advanced Biliary Tract Cancers.

Purpose: SWOG S1815 was a randomized, open label phase III trial, evaluating gemcitabine, nab-paclitaxel, and cisplatin (GAP) versus gemcitabine and cisplatin (GC) in patients with newly diagnosed advanced biliary tract cancers (BTCs).

Methods: Patients with newly diagnosed locally advanced unresectable or metastatic BTC, including intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC) and gallbladder carcinoma (GBC), were randomly assigned 2:1 to either GAP (gemcitabine 800 mg/m, cisplatin 25 mg/m, and nab-paclitaxel 100 mg/m intravenously once per day on days 1 and 8 of a 21-day cycle) or GC (gemcitabine 1,000 mg/m and cisplatin 25 mg/m intravenously once per day on days 1 and 8 of a 21-day cycle).

Results: Among 452 randomly assigned participants, 441 were eligible and analyzable, 67% with ICC, 16% with GBC, and 17% with ECC.

How dialysis frequency and duration impact uremic toxin and fluid removal: a pediatric perspective.

Three-weekly 4-h hemodialysis/hemodiafiltration (HD/HDF) per week has become the "standard HD/HDF" regimen in children across the globe, although increasingly criticized, since crucial determinants such as residual kidney function and patient preferences are not considered. As a consequence, several children fail to achieve adequate dialysis while on a "standard HD/HDF." In these circumstances, an extended dialysis prescription such as short daily (2-3 h/session, 5-7 days a week) or nocturnal HD/HDF (6-9 h/session, 3-5 days a week), either at home or in a dialysis center, may be considered.

Clinical and Genomic Features of Classical and Basal Transcriptional Subtypes in Pancreatic Cancer.

Purpose: Transcriptional profiling of pancreatic cancers has defined two main transcriptional subtypes: classical and basal. Initial data suggest shorter survival for patients with basal tumors and differing treatment sensitivity to FOLFIRINOX and gemcitabine plus nab-paclitaxel by transcriptional subtype.

Experimental Design: We examined 8,743 patients with RNA sequencing from pancreatic cancers performed at Caris Life Sciences.

A First-in-Human Study of Cinrebafusp Alfa, a HER2/4-1BB Bispecific Molecule, in Patients with HER2-Positive Advanced Solid Malignancies.

Purpose: 4-1BB (CD137) is a costimulatory immune receptor expressed on activated T cells, activated B cells, NK cells, and tumor-infiltrating lymphocytes, making it a promising target for cancer immunotherapy. Cinrebafusp alfa, a monoclonal antibody-like bispecific protein targeting HER2 and 4-1BB, aims to localize 4-1BB activation to HER2-positive tumors. This study evaluated the safety, tolerability, and preliminary efficacy of cinrebafusp alfa in patients with previously treated HER2-positive malignancies.

Safety and Efficacy of Cinacalcet in Children Aged Under 3 Years on Maintenance Dialysis.

Introduction: Secondary hyperparathyroidism (sHPT) is particularly severe in rapidly growing infants in dialysis. Although cinacalcet is effective and licensed in dialysis in children aged >3 years, its efficacy and safety for children aged <3 years is unknown.

Methods: We identified 26 children aged <3 years who were on dialysis and treated with cinacalcet between 2009 and 2021 in 8 European pediatric centers.

Calcium isotope composition in serum and urine for the assessment of bone mineral balance (BMB) - The Osteolabs post-market follow-up study.

To further explore the clinical applicability of the calcium (Ca) isotope marker (CIM), we determined the Ca/Ca isotope ratio in blood serum and urine. This ratio is expressed in the conventional δ-notation (as defined in the text below) specifically as CIM-serum for serum and as CIM-urine for urine. Our study tested the hypothesis that CIM values can differentiate between positive and negative bone mineral balance (BMB) across a diverse clinical population considering variables such as age, gender, and diet.

Changes in the cardiovascular risk profile in children approaching kidney replacement therapy.

Background: Despite significant cardiovascular (CV) morbidity in children on dialysis and after kidney transplantation, data on the evolution of CV damage in children with chronic kidney disease (CKD) approaching kidney replacement therapy (KRT) is unknown.

Methods: The burden, progression, and predictors of CV damage before KRT onset were explored in two prospective multicenter cohorts from Europe and Canada: Cardiovascular Comorbidity in Children with CKD (4C) and Haemodiafiltration, Heart and Height (3H) studies, conducted from 2009-19 and 2013-16, respectively. CV damage and risk factors were evaluated (i) cross sectionally at KRT-start (n = 248), and (ii) longitudinally over the 2-years preceding KRT start (n = 157; 331 patient-visits).

Factors influencing circuit lifetime in paediatric continuous kidney replacement therapies - results from the EurAKId registry.

Background: Continuous kidney replacement therapy (CKRT) has recently become the preferred kidney replacement modality for children with acute kidney injury (AKI). We hypothesise that CKRT technical parameters and treatment settings in addition to the clinical characteristics of patients may influence the circuit lifetime in children.

Methods: The study involved children included in the EurAKId registry (NCT02960867), who underwent CKRT treatment.