Citrate versus heparin anticoagulation in continuous renal replacement therapy in small children.

BACKGROUND: Citrate is preferred over heparin as an anticoagulant in adult continuous renal replacement therapy (CRRT). However, its potential adverse effects and data on use in CRRT in infants and toddlers is limited. We conducted a prospective study on using citrate in CRRT in critically ill small children. METHODS: Children who underwent CRRT with the smallest filter in our PICU between November 2011 and November 2016 were included. Both heparin and citrate were applied according to a strict protocol. Our primary outcome was circuit survival time. Secondary outcomes were alkalosis, citrate toxicity, and number of red blood cell transfusions. RESULTS: Heparin was used in six patients (121 circuits, total CRRT time 3723 h). Citrate was used in 14 patients (105 circuits, total CRRT time 4530 h). Median circuit survival time with heparin was 21 h (IQR 14.5-27.5) compared to 45.2 h (IQR 37.5-52.8) with citrate (p < 0.001). Actual administered effluent dose compared to prescribed dose was 85% (IQR 69-98%) with heparin compared to 92% (IQR 88-98%) with citrate (p = 0.31). No patient treated with citrate developed citrate toxicity. No other differences in electrolytes were found between the two CRRT regimes. In the heparin group, a median of 6.5 units of red blood cells (IQR 1.5-23.8) were given during CRRT, compared to three in the citrate group (IQR 2.0-5.0, p = 0.12). CONCLUSIONS: Use of regional citrate significantly prolongs circuit survival time and thereby should increase CRRT efficiency when compared to heparin. In addition, citrate appears safe for CRRT in critically ill small children.

Long term follow-up of HNPCC gene mutation carriers: compliance with screening and satisfaction with counseling and screening procedures.

Hereditary non polyposis colorectal cancer (HNPCC) is a hereditary predisposition to colorectal and endometrial cancer, caused by mutations of the mismatch repair (MMR) genes MSH2, MLH1 and MSH6. Regular colonoscopy reduces the incidence of colorectal cancer in mutation carriers dramatically. The aim of this study was to evaluate the use of colonoscopy by proven HNPCC mutation carriers. We also evaluated the satisfaction with the counseling and screening procedures at the long term. A questionnaire survey was performed among 94 proven MMR gene mutation carriers. Data were analyzed using univariate and multivariate analysis. The average time of follow-up was 3,5 years (range 0.5-8.5 years). The response rate was 74%. The proportion of unaffected mutation carriers under colonoscopic screening increased from 31 to 88% upon genetic testing, and for gynecological screening from 17 to 69%. However, more than half of the responders experienced colonoscopy as unpleasant or painful. About 97% felt well informed during counseling, and 88% felt sufficiently supported. Ten percent of the responders reported a high cancer worry that was significantly (P = 0.007) associated with a high perceived cancer risk. Six responders (9%) regretted being tested. Remarkably, of 4 of these 6 a close relative died recently of cancer. Problems with obtaining a disability or life insurance or mortgage were experienced by 4 out 10 healthy carriers opting for these services. In conclusion, genetic testing for HNPCC considerably improves compliance for screening, which will result in a reduction of HNPCC-related cancer morbidity and mortality in mutation carriers. Most HNPCC gene mutation carriers cope well with their cancer susceptibility on the long term.

Non-pheochromocytoma (PCC)/paraganglioma (PGL) tumors in patients with succinate dehydrogenase-related PCC-PGL syndromes: a clinicopathological and molecular analysis.

OBJECTIVE: Although the succinate dehydrogenase (SDH)-related tumor spectrum has been recently expanded, there are only rare reports of non-pheochromocytoma/paraganglioma tumors in SDHx-mutated patients. Therefore, questions still remain unresolved concerning the aforementioned tumors with regard to their pathogenesis, clinicopathological phenotype, and even causal relatedness to SDHx mutations. Absence of SDHB expression in tumors derived from tissues susceptible to SDH deficiency is not fully elucidated. DESIGN AND METHODS: Three unrelated SDHD patients, two with pituitary adenoma (PA) and one with papillary thyroid carcinoma (PTC), and three SDHB patients affected by renal cell carcinomas (RCCs) were identified from four European centers. SDHA/SDHB immunohistochemistry (IHC), SDHx mutation analysis, and loss of heterozygosity analysis of the involved SDHx gene were performed on all tumors. A cohort of 348 tumors of unknown SDHx mutational status, including renal tumors, PTCs, PAs, neuroblastic tumors, seminomas, and adenomatoid tumors, was investigated by SDHB IHC. RESULTS: Of the six index patients, all RCCs and one PA displayed SDHB immunonegativity in contrast to the other PA and PTC. All immunonegative tumors demonstrated loss of the WT allele, indicating bi-allelic inactivation of the germline mutated gene. Of 348 tumors, one clear cell RCC exhibited partial loss of SDHB expression. CONCLUSIONS: These findings strengthen the etiological association of SDHx genes with pituitary neoplasia and provide evidence against a link between PTC and SDHx mutations. Somatic deletions seem to constitute the second hit in SDHB-related renal neoplasia, while SDHx alterations do not appear to be primary drivers in sporadic tumorigenesis from tissues affected by SDH deficiency.

A Delphi study to determine the European core curriculum for Master programmes in genetic counselling.

Genetic counsellors have been working in some European countries for at least 30 years. Although there are great disparities between the numbers, education, practice and acceptance of these professionals across Europe, it is evident that genetic counsellors and genetic nurses in Europe are working autonomously within teams to deliver patient care. The aim of this study was to use the Delphi research method to develop a core curriculum to guide the educational preparation of these professionals in Europe. The Delphi method enables the researcher to utilise the views and opinions of a group of recognised experts in the field of study; this study consisted of four phases. Phases 1 and 4 consisted of expert workshops, whereas data were collected in phases 2 and 3 (n=35) via online surveys. All participants in the study were considered experts in the field of genetic counselling. The topics considered essential for genetic counsellor training have been organised under the following headings: (1) counselling; (2) psychological issues; (3) medical genetics; (4) human genetics; (5) ethics, law and sociology; (6) professional practice; and (7) education and research. Each topic includes the knowledge, skills and attitudes required to enable genetic counsellors to develop competence. In addition, it was considered by the experts that clinical practice should comprise 50% of the educational programme. The core Master programme curriculum will enable current courses to be assessed and inform the design of future educational programmes for European genetic counsellors.