Supplementary Material for: Whole-Exome Sequencing Reveals FAT4 Mutations in a Clinically Unrecognizable Patient with Syndromic CAKUT: A Case Report

We present the case of a patient of Macedonian origin with unilateral renal agenesis and ureterovesical junction obstruction in combination with further abnormalities including midface hypoplasia, scoliosis as well as camptodactyly of one toe. Whole-exome sequencing analysis revealed compound heterozygous variants in the <i>FAT4</i> gene. Recessive variants in <i>FAT4</i> are a known cause of van Maldergem syndrome (VMS) in which congenital anomalies of the kidney and urinary tract are a less characteristic but common feature. The initial presentation of our patient was not clinically recognizable. However, in view of the molecular findings, the most likely diagnosis is a mild manifestation of VMS. Only very few publications have reported patients with VMS and mutations in <i>FAT4 </i>to date. With this case, we hope to provide further insight into the phenotypic variability of this syndrome

Interprofessional consensus regarding design requirements for liquid-based perinatal life support (PLS) technology

Liquid-based perinatal life support (PLS) technology will probably be applied in a first-in-human study within the next decade. Research and development of PLS technology should not only address technical issues, but also consider socio-ethical and legal aspects, its application area, and the corresponding design implications. This paper represents the consensus opinion of a group of healthcare professionals, designers, ethicists, researchers and patient representatives, who have expertise in tertiary obstetric and neonatal care, bio-ethics, experimental perinatal animal models for physiologic research, biomedical modeling, monitoring, and design. The aim of this paper is to provide a framework for research and development of PLS technology. These requirements are considering the possible respective user perspectives, with the aim to co-create a PLS system that facilitates physiological growth and development for extremely preterm born infants.Developmen

Interprofessional Consensus Regarding Design Requirements for Liquid-Based Perinatal Life Support (PLS) Technology

Liquid-based perinatal life support (PLS) technology will probably be applied in a first-in-human study within the next decade. Research and development of PLS technology should not only address technical issues, but also consider socio-ethical and legal aspects, its application area, and the corresponding design implications. This paper represents the consensus opinion of a group of healthcare professionals, designers, ethicists, researchers and patient representatives, who have expertise in tertiary obstetric and neonatal care, bio-ethics, experimental perinatal animal models for physiologic research, biomedical modeling, monitoring, and design. The aim of this paper is to provide a framework for research and development of PLS technology. These requirements are considering the possible respective user perspectives, with the aim to co-create a PLS system that facilitates physiological growth and development for extremely preterm born infants

Clinical predictors of decline in nutritional parameters over time in ESRD

Item does not contain fulltextBACKGROUND AND OBJECTIVES: Inflammation and malnutrition are important features in patients with ESRD; however, data on changes in these parameters over time are scarce. This study aimed to gain insight into changes over time in serum albumin, body mass index, high-sensitivity C-reactive protein, and IL-6 in patients with ESRD and aimed to identify clinical risk factors for deterioration of these parameters. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Data were analyzed from the Convective Transport Study, a randomized controlled trial conducted from June 2004 to January 2011, in which 714 patients with chronic ESRD were randomized to either online hemodiafiltration or low-flux hemodialysis. Albumin and body mass index were measured up to 6 years and predialysis C-reactive protein and IL-6 were measured up to 3 years in a subset of 405 participants. Rates of change in these parameters over time were estimated across strata of predefined risk factors with linear mixed-effects models. RESULTS: Albumin and body mass index decreased and C-reactive protein and IL-6 increased over time. For every incremental year of age at baseline, the yearly excess decline in albumin was 0.003 g/dl (-0.004 to -0.002; P<0.001) and the excess decline in body mass index was 0.02 kg/m(2) per year (-0.02 to -0.01; P<0.001). In patients with diabetes mellitus, there was a yearly excess decline of 0.05 g/dl in albumin (-0.09 to -0.02; P=0.002). Compared with women, men had an excess decline of 0.03 g/dl per year in albumin (-0.06 to -0.001; P=0.05) and an excess increase of 11.6% per year in IL-6 (0.63%-23.6%; P=0.04). CONCLUSIONS: Despite guideline-based care, all inflammatory and nutritional parameters worsened over time. The deterioration of some of these parameters was more pronounced in men, older patients, and patients with diabetes mellitus. Special focus on the nutritional status of at-risk patients by individualizing medical care might improve their prognosis

Poor Compliance with Guidelines on Anemia Treatment in a Cohort of Chronic Hemodialysis Patients

Item does not contain fulltextBACKGROUND/AIMS: Guidelines for the management of anemia and iron deficiency in chronic hemodialysis (HD) patients have been developed to standardize therapy and improve clinical outcome. The present study evaluated compliance with anemia guidelines and investigated whether differences between centers were present. METHODS: Data on anemia management from patients in the baseline cohort of the CONTRAST study (NCT00205556) were analyzed. 598 chronic HD patients (62% male, age 63.6 +/- 14.0 years) from 26 Dutch dialysis centers were included. RESULTS: Mean hemoglobin (Hb) level was 11.9 +/- 1.3 g/dl and Hb was >/=11.0 g/dl in 81% of the patients. Compliance with all anemia targets (Hb 11.0-12.0 g/dl, transferrin saturation ratio >/=20%, ferritin 100-500 ng/ml) was reached in 11.6% (95% CI 7.8-17.0) of the patients, with a wide range among centers (4-26%, adjusted for case mix, treatment-related factors and center-specific characteristics). CONCLUSION: Compliance with anemia targets in stable HD patients was poor and showed a wide variation between treatment facilities

Whole-Exome Sequencing Identifies Causative Mutations in Families with Congenital Anomalies of the Kidney and Urinary Tract.

Item does not contain fulltextBACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUT) are the most prevalent cause of kidney disease in the first three decades of life. Previous gene panel studies showed monogenic causation in up to 12% of patients with CAKUT. METHODS: We applied whole-exome sequencing to analyze the genotypes of individuals from 232 families with CAKUT, evaluating for mutations in single genes known to cause human CAKUT and genes known to cause CAKUT in mice. In consanguineous or multiplex families, we additionally performed a search for novel monogenic causes of CAKUT. RESULTS: In 29 families (13%), we detected a causative mutation in a known gene for isolated or syndromic CAKUT that sufficiently explained the patient's CAKUT phenotype. In three families (1%), we detected a mutation in a gene reported to cause a phenocopy of CAKUT. In 15 of 155 families with isolated CAKUT, we detected deleterious mutations in syndromic CAKUT genes. Our additional search for novel monogenic causes of CAKUT in consanguineous and multiplex families revealed a potential single, novel monogenic CAKUT gene in 19 of 232 families (8%). CONCLUSIONS: We identified monogenic mutations in a known human CAKUT gene or CAKUT phenocopy gene as the cause of disease in 14% of the CAKUT families in this study. Whole-exome sequencing provides an etiologic diagnosis in a high fraction of patients with CAKUT and will provide a new basis for the mechanistic understanding of CAKUT.1 september 201