Brain imaging in children with neonatal cholestatic liver disease: A systematic review.

AIM: To determine if children with neonatal cholestatic liver disease had concurrent and later findings on brain imaging studies that could be attributed and the cholestasis to contribute to the understanding of the impaired neuropsychological development. METHODS: Ovid MEDLINE and EMBASE were searched on July 21, 2022, and updated on March 26, 2023. Studies with children under 18 years of age with neonatal cholestasis and a brain scan at the time of diagnosis or later in life were included. Excluded studies were non-English, non-human, reviews or conference abstracts. Data were extracted on demographics, brain imaging findings, treatment and outcome. The results were summarised by disease categories. Risk of bias was assessed using JBI critical appraisal tools. RESULTS: The search yielded 12 011 reports, of which 1261 underwent full text review and 89 were eligible for inclusion. Haemorrhage was the most common finding, especially in children with bile duct obstruction, including biliary atresia. Some findings were resolved after liver transplantation. CONCLUSION: Children with neonatal cholestasis had changes in brain imaging, which might play a role in impaired neuropsychological development, but longitudinal clinical research with structured assessment is needed to better qualify the aetiology of the impairment.

Epidemiological Study of Malignant Paediatric Liver Tumours in Denmark 1985-2020.

BACKGROUND: Malignant liver tumours in children are rare and national outcomes for this tumour entity are rarely published. This study mapped paediatric liver tumours in Denmark over 35 years and reported on the incidence, outcomes and long-term adverse events. METHODS: We identified all liver tumours from the Danish Childhood Cancer Registry and reviewed the case records for patient and tumour characteristics, treatment and clinical outcome. RESULTS: We included 79 patients in the analyses. Overall crude incidence was ~2.29 per 1 million children (<15 yr) per year, with 61 hepatoblastomas (HB), 9 hepatocellular carcinomas and 9 other hepatic tumours. Overall 5-year survival was 84%, 78% and 44%, respectively. Nine patients had underlying liver disease or predisposition syndrome. Seventeen children underwent liver transplantation, with two late complications, biliary stenosis and liver fibrosis. For HB, age ≥ 8 years and diagnosis prior to 2000 were significant predictors of a poorer outcome. Adverse events included reduced renal function in 10%, reduced cardiac function in 6% and impaired hearing function in 60% (19% needed hearing aids). Behavioural conditions requiring additional support in school were registered in 10 children. CONCLUSIONS: In Denmark, incidences of malignant liver tumours during the last four decades have been increasing, as reported in the literature. HB survival has improved since the year 2000 and is comparable with international results. Reduced hearing is the major treatment-related side effect and affects approximately 60% of patients.

Towards a model of biliary atresia - Pilot feasibility study in newborn piglets.

Biliary atresia (BA) is a rare congenital liver disease with unknown etiology, and it is the most common indication for liver transplantation in children. As BA infants suffer from intestinal malabsorption and neurodevelopmental deficits, it is necessary to identify optimal medical and nutritional strategies using appropriate neonatal animal models. We aim to determine the feasibility of using newborn piglets with surgically induced cholestasis (bile duct ligation (BDL)) to mimic clinical features of BA. Six piglets were subjected to abdominal surgery on day 4 after birth. The bile ducts were ligated, and the piglet were followed for up to 12 days. On day 12 the piglets were subjected to a hepatobiliary scintigraphy using the tracer radiolabeled Technetium(99m-tc)-mebrofenin, and blood samples were collected for biochemical profiling. Of the six piglets, hepatobiliary scintigraphy verified that two piglets (BDL) had no excretion of bile into the duodenum, i.e. full cholestasis with a hepatic extraction fraction of 84-87% and clearance time of 230-318 min. One piglet (SHAM) had bile excretion to the duodenum. In accordance with this, the BDL piglets had steatorrhea, and increased levels of bilirubin and gammaglutamyl transferase (GGT). The last three piglets were euthanized due to bile leakage or poor growth. Surgically induced cholestasis in young piglets, may offer an animal model that displays clinical characteristics of biliary atresia, including malabsorption, hyperbilirubinaemia, increased GGT and reduced hepatic excretory function. Following refinement, this animal model may be used to optimize feeding strategies to secure optimal nutrition and neurodevelopment for neonatal cholestasis/BA patients.

Incidence of Isolated Biliary Atresia during the COVID Lockdown in Europe: Results from a Collaborative Project by RARE-Liver.

BACKGROUND: Biliary atresia (BA) is a rare cholangiopathy where one of the proposed aetiological mechanisms is an infectious viral trigger. Coronavirus disease-19 (COVID) lockdown restrictions were implemented to reduce the transmission of infections. Strictness of lockdown varied across European countries. This study aimed to investigate if there was an association between strictness of lockdown and change in isolated BA (IBA) incidence in Europe. METHODS: We approached European centres involved in the European Reference Network RARE-LIVER. We included IBA patients born between 2015 and June 2020. We calculated the number of IBA patients born per centre per month. The Stringency Index (SI) was used as lockdown strictness indicator. The association between percentage change of mean number of IBA patients born per month and the SI was assessed. RESULTS: We included 412 IBA patients from thirteen different centres. The median number of patients per month did not change: 6 (1-15) pre-lockdown and 7 (6-9) during lockdown (p = 0.34). There was an inverse association between SI and percentage change in IBA (B = -0.73, p = 0.03). Median age at Kasai portoenterostomy (days) did not differ between time periods (51 (9-179) vs. 53 (19-126), p = 0.73). CONCLUSION: In this European study, a stricter COVID-lockdown was seemingly accompanied by a simultaneous larger decrease in the number of IBA patients born per month in the lockdown. Results should be interpreted with caution due to the assumptions and limitations of the analysis.

Cholestasis alters brain lipid and bile acid composition and compromises motor function in neonatal piglets.

Infants with neonatal cholestasis are prone to neurodevelopmental deficits, however, the underlying pathogenesis is unclear. Lipid malabsorption and accumulation of potentially neurotoxic molecules in the blood such as bile acids are important yet relatively unexplored pathways. Here, we developed a translational piglet model to understand how the molecular bile acid and lipid composition of the brain is affected by this disease and relates to motor function. Piglets (8-days old) had bile duct ligation or sham surgery and were fed a formula diet for 3 weeks. Alongside sensory-motor deficits observed in bile duct-ligated animals, we found a shift toward a more hydrophilic and conjugated bile acid profile in the brain. Additionally, comprehensive lipidomics of the cerebellum revealed a decrease in total lipids including phosphatidylinositols and phosphatidylserines and increases in lysophospholipid species. This was paralleled by elevated cerebellar expression of genes related to inflammation and tissue damage albeit without significant impact on the brain transcriptome. This study offers new insights into the developing brain's molecular response to neonatal cholestasis indicating that bile acids and lipids may contribute in mediating motor deficits.

Room for improvement in maternity care. / Fødselsomsorgen kan bli bedre.

Adverse events still occur in maternity care, and many could be avoided. We must be better at learning from our own mistakes.

Adverse events reporting by obstetric units in Norway as part of their quality assurance and patient safety work: an analysis of practice.

BACKGROUND: The Norwegian Board of Health Supervision aims to contribute to the improvement of quality and patient safety in the healthcare services. Planned audits were performed to investigate how 12 selected Norwegian obstetric units reported and analyzed adverse events as the part of their quality assurance and patient safety work. METHODS: Serious adverse events coded as birth asphyxia, shoulder dystocia and severe postpartum hemorrhage that occurred during 2014 (the most recent year for which the quality assured data were available) were obtained from the Medical Birth Registry of Norway. The obstetric units were asked to submit medical records, internal adverse events reports, and their internal guidelines outlining which events should be reported to the quality assurance system. We identified the adverse events at each obstetric unit that were reported internally and/or to the central authorities. Two obstetricians carried out an evaluation of each event reported. RESULTS: Five hundred fifty-three serious adverse events were registered among 17,323 births that took place at the selected units. Twenty-one events were excluded because of incorrect coding or missing information. Eight events were registered in more than one category, and these were distributed to the category directly related to injury or adverse outcome. Nine of twelve (75 %) obstetric units had written guidelines describing which events should be reported. The obstetric units reported 49 of 524 (9.3 %) serious adverse events in their internal quality assurance system and 39 (7.4 %) to central authorities. Of the very serious adverse events, 29 of 149 (19.4 %) were reported. Twenty-three of 49 (47 %) reports did not contain relevant assessments or proposals for improving quality and patient safety. CONCLUSIONS: This study showed that adverse event reporting and analyses by Norwegian obstetric units, as a part of quality assurance and patient safety work, are suboptimal. The reporting culture and compliance with guidelines need to be improved substantially for better safety in patient care, risk mitigation and clinical quality assurance.

How common is substandard obstetric care in adverse events of birth asphyxia, shoulder dystocia and postpartum hemorrhage? Findings from an external inspection of Norwegian maternity units.

INTRODUCTION: The Norwegian Board of Health Supervision inspects healthcare institutions to ensure safety and quality of health and welfare services. A planned inspection of 12 maternity units aimed to investigate the practice of obstetric care in the case of birth asphyxia, shoulder dystocia and severe postpartum hemorrhage. MATERIAL AND METHODS: The inspection was carried out at two large, four medium and six small maternity units in Norway in 2016 to investigate adverse events that occurred between 1 January and 31 December 2014. Six of them were selected as control units. The Norwegian Board of Health Supervision searched the Medical Birth Registry of Norway to identify adverse events in each of the categories and then requested access to the medical records for all patients identified. Information about guidelines, formal teaching and simulation training at each unit was obtained by sending a questionnaire to the obstetrician in charge of each maternity unit. RESULTS: The obstetric units inspected had 553 serious adverse events of birth asphyxia, shoulder dystocia or severe postpartum hemorrhage among 17 323 deliveries. Twenty-nine events were excluded from further analysis due to erroneous coding or missing data in the patients' medical records. We included 524 cases (3.0% of all deliveries) of adverse events in the final analysis. Medical errors caused by substandard care were present in 295 (56.2%) cases. There was no difference in the prevalence of substandard care among the maternity units according to their size. Surprisingly, we found significantly fewer cases with substandard care in the units which the supervisory authorities considered particularly risky before the inspection, compared with the control units. Seven of the 12 units had regular formal teaching and training arrangements for obstetric healthcare personnel as outlined in the national guidelines. CONCLUSIONS: Prevalence of adverse events was 3% and similar in all maternity units irrespective of their size. A breach in the standard of care was observed in 56.2% of cases and almost half of the maternity units did not follow national recommendations regarding teaching and practical training of obstetric personnel, suggesting that they should focus on implementing guidelines and training their staff.

ERNICA guidelines for the management of rectosigmoid Hirschsprung's disease.

BACKGROUND: Hirschsprung's disease (HSCR) is a serious congenital bowel disorder with a prevalence of 1/5000. Currently, there is a lack of systematically developed guidelines to assist clinical decision-making regarding diagnostics and management. AIMS: This guideline aims to cover the diagnostics and management of rectosigmoid HSCR up to adulthood. It aims to describe the preferred approach of ERNICA, the European Reference Network for rare inherited and congenital digestive disorders. METHODS: Recommendations within key topics covering the care pathway for rectosigmoid HSCR were developed by an international workgroup of experts from 8 European countries within ERNICA European Reference Network from the disciplines of surgery, medicine, histopathology, microbiology, genetics, and patient organization representatives. Recommendation statements were based on a comprehensive review of the available literature and expert consensus. AGREE II and GRADE approaches were used during development. Evidence levels and levels of agreement are noted. RESULTS: Thirty-three statements within 9 key areas were generated. Most recommendations were based on expert opinion. CONCLUSION: In rare or low-prevalence diseases such as HSCR, there remains limited availability of high-quality clinical evidence. Consensus-based guidelines for care are presented.

In Vitro Investigation of the Dependency Between Abutment Length and Implant Stability Quotient (ISQ) for Stability Measurements on Bone Anchored Hearing Implant Systems.

HYPOTHESIS: The investigation aimed at measuring the relation between abutment length and Implant Stability Quotient (ISQ) for stability measurements on two types of bone-anchored hearing implant systems. BACKGROUND: Measuring bone-anchored hearing implant stability using the ISQ has the inherent limitation that the measurement is dependent on the length of the abutment used on the implant. This dependency has not earlier been analyzed in depth. Therefore, ISQ measurements for different abutment lengths cannot be directly compared if a patient needs a change of abutment or when evaluating different patients in a scientific setting. METHODS: The dependency of ISQ on abutment length for Cochlear BI300 (Cochlear Nordic AB, Mölnlycke, Sweden) and Ponto Wide Implant (Oticon Medical AB, Askim, Swden) was measured using a temporal bone model and a plaster model. ISQ at abutment level was compared with the corresponding ISQ at implant level and results were analyzed by multiple linear regression. RESULTS: The ISQ dependency on abutment length was -3.5 ISQ/mm (95% CI: -3.7 to -3.4) (Cochlear BI300 implant) and -2.9 ISQ/mm (95% CI: -3.0 to -2.7) (Oticon Wide Implant). CONCLUSION: The dependency of ISQ on abutment length for two types of bone-anchored hearing implant systems has been established empirically. This knowledge enables clinicians to continue monitoring the ISQ for a patient after a change of abutment and enables researchers to compare ISQ between patients in a clinical study.

Management strategies and treatment results of pediatric choledochal malformations in the Nordic countries.

BACKGROUND: Incidence and long-term outcomes of choledochal malformations (CMs) in children remain unclear. METHODS: Clinical characteristics, operative details, complications, and follow-up data were collected from eight pediatric surgical centers in Sweden, Norway, Denmark, and Finland, which also answered a questionnaire addressing management practices. RESULTS: During 2000-2017, 126 pediatric CMs were diagnosed, corresponding an incidence of 1:37,400. Diagnostic, treatment, and follow-up practices varied markedly. Of patients with complete clinical data (n = 119), 85% and 11% had type I and IV CMs and were managed by open hepaticojejunostomy at median age of 2.5 (interquartile range 0.46-5.8) years. Associated malformations were more common in fusiform and type IV (23%) than cystic CMs (8%, p = 0.043). Pancreaticobiliary maljunction was more frequently confirmed in patients presenting with pancreatitis (26% vs. 7%, p = 0.005) and with fusiform CMs (56% vs. 25%, p = 0.001). Cholangitis/pancreatitis episodes, occurring in 12% during postoperative follow-up of 4.0 (2.0-7.9) years, associated with longer surveillance (OR 1.32, 95% CI 1.13-1.54, p < 0.001). However, only two thirds of centers continued follow-up until adulthood. No malignancies were reported. CONCLUSIONS: CM incidence was higher than traditionally reported among Western populations. Although open hepaticojejunostomy carries good short-term outcomes, long-term morbidity is noteworthy. Standardized evidence-based management strategies and long-term follow-up are encouraged.

An evaluation by the Norwegian Health Care Supervision Authorities of events involving death or injuries in maternity care.

INTRODUCTION: We aimed to determine how serious adverse events in obstetrics were assessed by supervision authorities. MATERIAL AND METHODS: We selected cases investigated by supervision authorities during 2009-2013. We analyzed information about who reported the event, the outcomes of the mother and infant, and whether events resulted from errors at the individual or system level. We also assessed whether the injuries could have been avoided. RESULTS: During the study period, there were 303 034 births in Norway, and supervision authorities investigated 338 adverse events in obstetric care. Of these, we studied 207 cases that involved a serious outcome for mother or infant. Five mothers (2.4%) and 88 infants (42.5%) died. Of the 207 events reported to the supervision authorities, patients or relatives reported 65.2%, hospitals reported 39.1%, and others reported 4.3%. In 8.7% of cases, events were reported by more than 1 source. The supervision authority assessments showed that 48.3% of the reported cases involved serious errors in the provision of health care, and a system error was the most common cause. We found that supervision authorities investigated significantly more events in small and medium-sized maternity units than in large units. Eighteen health personnel received reactions; 15 were given a warning, and 3 had their authority limited. We determined that 45.9% of the events were avoidable. CONCLUSIONS: The supervision authorities investigated 1 in 1000 births, mainly in response to complaints issued from patients or relatives. System errors were the most common cause of deficiencies in maternity care.

Outcomes of biliary atresia in the Nordic countries - a multicenter study of 158 patients during 2005-2016.

BACKGROUND/PURPOSE: Biliary atresia is the most common reason for newborn cholestasis and pediatric liver transplantation. Even after normalization of serum bilirubin after portoenterostomy, most patients require liver transplantation by adulthood due to expanding fibrosis. We addressed contemporary outcomes of biliary atresia in the Nordic countries. METHODS: Data on center and patients characteristics, diagnostic practices, surgical treatment, adjuvant medical therapy after portoenterostomy, follow-up and outcomes were collected from all the Nordic centers involved with biliary atresia care during 2005-2016. RESULTS: Of the 154 patients, 148 underwent portoenterostomy mostly by assigned surgical teams at median age of 64 (interquartile range 37-79) days, and 95 patients (64%) normalized their serum bilirubin concentration while living with native liver. Postoperative adjuvant medical therapy, including steroids, ursodeoxycholic acid and antibiotics was given to 137 (93%) patients. Clearance of jaundice associated with young age at surgery and favorable anatomic type of biliary atresia, whereas annual center caseload >3 patients and diagnostic protocol without routine liver biopsy predicted early performance of portoenterostomy. The cumulative 5-year native liver and overall survival estimate was 53% (95% CI 45-62) and 88% (95% CI 83-94), respectively. Portoenterostomy age <65days and annual center caseload >3 patients were predictive for long-term native liver survival, while normalization of serum bilirubin after portoenterostomy was the major predictor of both native liver and overall 5-year survival. CONCLUSIONS: The outcomes of biliary atresia in the Nordic countries compared well with previous European studies. Further improvement should be pursued by active measures to reduce patient age at portoenterostomy. RETROSPECTIVE PROGNOSIS STUDY: Level II.

Are stipulated requirements for the quality of maternity care complied with? / Følges fastsatte kvalitetskrav i fødselsomsorgen?

BACKGROUND: The Directorate of Health's national guide Et trygt fødetilbud ­ kvalitetskrav til fødselsomsorgen [A safe maternity service ­ requirements regarding the quality of maternity care] was published in December 2010 and was intended to provide a basis for an improved and more predictable maternity service. This article presents data from the maternity institutions on compliance with the quality requirements, including information on selection, fetal monitoring, organisation, staffing and competencies. MATERIAL AND METHOD: The information was acquired with the aid of an electronic questionnaire in the period January­May 2015. The form was sent by e-mail to the medical officer in charge at all maternity units in Norway as at 1 January 2015 (n=47). RESULTS: There was a 100 % response to the questionnaire. The criteria for selecting where pregnant women should give birth were stated to be in conformity with the quality requirements. Some maternity institutions failed to describe the areas of responsibilities of doctors and midwives (38.5 % and 15.4 %, respectively). Few institutions recorded whether the midwife was present with the patient during the active phase. Half of the maternity departments (level 2 birth units) reported unfilled doctors' posts, and a third of the university hospitals/central hospitals (level 1 birth units) reported a severe shortage of locum midwives. Half of the level 2 birth units believed that the quality requirements had resulted in improved training, but reported only a limited degree of interdisciplinary or mandatory instruction. INTERPRETATION: The study reveals that there are several areas in which the health enterprises have procedures that conform to national quality requirements, but where it is still unclear whether they are observed in practice. Areas for improvement relate to routines describing areas of responsibility, availability of personnel resources and staff training.

Differentiated effects of deep brain stimulation and medication on somatosensory processing in Parkinson's disease.

OBJECTIVES: Deep brain stimulation (DBS) and dopaminergic medication effectively alleviate the motor symptoms in Parkinson's disease (PD) patients, but their effects on the sensory symptoms of PD are still not well understood. To explore early somatosensory processing in PD, we recorded magnetoencephalography (MEG) from thirteen DBS-treated PD patients and ten healthy controls during median nerve stimulation. METHODS: PD patients were measured during DBS-treated, untreated and dopaminergic-medicated states. We focused on early cortical somatosensory processing as indexed by N20m, induced gamma augmentation (31-45Hz and 55-100Hz) and induced beta suppression (13-30Hz). PD patients' motor symptoms were assessed by UPDRS-III. RESULTS: Using Bayesian statistics, we found positive evidence for differentiated effects of treatments on the induced gamma augmentation (31-45Hz) with highest gamma in the dopaminergic-medicated state and lowest in the DBS-treated and untreated states. In contrast, UPDRS-III scores showed beneficial effects of both DBS and dopaminergic medication on the patients' motor symptoms. Furthermore, treatments did not affect the amplitude of N20m. CONCLUSIONS: Our results suggest differentiated effects of DBS and dopaminergic medication on cortical somatosensory processing in PD patients despite consistent ameliorating effects of both treatments on PD motor symptoms. SIGNIFICANCE: The differentiated effect suggests differences in the effect mechanisms of the two treatments.

Bone Anchored Hearing Implant Surgery: 1 Year Follow-Up Data Shows No Effect of Hydroxyapatite Coating on Soft Tissue Reaction After Loading at 1 Week.

OBJECTIVE: To assess postoperative skin complications around a bone anchored hearing implant (BAHI) abutment coated with hydroxyapatite and loaded after 1 week. DESIGN: Single center, prospective cohort study of 25 adults with expected normal skin and bone quality. INTERVENTION: Implantation of the Baha BA400 hydroxyapatite coated implant system using a linear incision technique without soft tissue reduction. Abutments with lengths of 8 mm (n = 9), 10 mm (n = 11), and 12 mm (n = 5) were used. The implants were loaded after 7 days (n = 23), 8 days (n = 1), and 12 days (n = 1). MAIN OUTCOME MEASURES: Soft tissue evaluation (Holger's score, skin overgrowth, pain, numbness) at 7 (±2), 14 (±3), and 30 (±7) days and 3 months (±14 days), 6 months (±14 days), and 12 months (±30 days). The results were compared with a historic control group. RESULTS: Twenty five patients were included, 23 could be followed up for 1 year. In 93.8% of the visits, patients had a Holger's score less than or equal to 1. One patient needed revision surgery due to skin overgrowth. 18.8% of the patients experienced mild pain during follow-up, primarily during the first month. Sensibility loss was very limited. Compared with similar patients having the smooth titanium abutment (loaded at 2 wk), there was a slightly increased level of short-term soft tissue reaction. CONCLUSION: The study shows a small, non-detrimental, negative effect on short-term soft tissue status after loading of the implant at 7 days. No positive effect from the hydroxyapatite coating could be demonstrated for the long-term soft tissue status.

Successful Loading of a Bone-Anchored Hearing Implant at 1 Week After Surgery.

OBJECTIVE: To assess implant stability and safety of loading a bone-anchored implant 1 week after surgery. The patients were loaded at 1 week for fast rehabilitation and ease of logistics. DESIGN: Single center, prospective cohort study of 25 adults with expected normal skin and bone quality. INTERVENTION: Implantation of the Baha BA400 implant system using a linear incision technique without skin thinning. Abutment lengths of 8, 10, and 12 mm were used. MAIN OUTCOME MEASURES: Implant stability quotient (ISQ) 0, 7, 14, 30 days and 3, 6, and 12 months postoperatively. RESULTS: Twenty-five patients were included, 23 could be followed up for 1 year. Mean ISQ was increasing throughout the observation period with no sign of adverse influence from the early loading. No implants were lost or clinically unstable. Individual ISQ curves fall in two categories-continually increasing ISQ or increasing ISQ with initial dip. ISQ for patients in the initial dip group eventually increased despite the early and continued loading. CONCLUSION: Loading of the implant system under study 1 week after surgery have been successful for 25 patients with expected normal bone quality followed up for 1 year. No implants were lost. All individual ISQ were increasing throughout the study period. The early loading of the implant under study does not seem to influence the osseointegration.

Genetic Variations in the Human G Protein-coupled Receptor Class C, Group 6, Member A (GPRC6A) Control Cell Surface Expression and Function.

GPRC6A is a G protein-coupled receptor activated by l-amino acids, which, based on analyses of knock-out mice, has been suggested to have physiological functions in metabolism and testicular function. The human ortholog is, however, mostly retained intracellularly in contrast to the cell surface-expressed murine and goldfish orthologs. The latter orthologs are Gq-coupled and lead to intracellular accumulation of inositol phosphates and calcium release. In the present study we cloned the bonobo chimpanzee GPRC6A receptor, which is 99% identical to the human receptor, and show that it is cell surface-expressed and functional. By analyses of chimeric human/mouse and human/bonobo receptors, bonobo receptor mutants, and the single nucleotide polymorphism database at NCBI, we identify an insertion/deletion variation in the third intracellular loop responsible for the intracellular retention and lack of function of the human ortholog. Genetic analyses of the 1000 genome database and the Inter99 cohort of 6,000 Danes establish the distribution of genotypes among ethnic groups, showing that the cell surface-expressed and functional variant is much more prevalent in the African population than in European and Asian populations and that this variant is partly linked with a stop codon early in the receptor sequence (rs6907580, amino acid position 57). In conclusion, our data solve a more than decade-old question of why the cloned human GPRC6A receptor is not cell surface-expressed and functional and provide a genetic framework to study human phenotypic traits in large genome sequencing projects linked with physiological measurement and biomarkers.

Hepatobiliary scintigraphy for early diagnosis of biliary atresia.

INTRODUCTION: The aim of this study was to evaluate the validity of (99m)Technetium-trimethylbromo-iminodiacetic acid hepatobiliary scintigraphy (HS) for the diagnosis of biliary atresia (BA). METHODS: From January 2005 to December 2009, a total of 47 infants with conjugated hyperbilirubinaemia (> 20 micromol/l total bilirubin of which 20% is conjugated) underwent HS. BA was suspected if no tracer was visualised in the gut 24 hours post-injection. The results of the HSs were compared with the gold standard, laparotomy with antegrade cholangiography findings. RESULTS: Considering the final diagnosis based on the gold standard, the sensitivity, specificity, positive predictive value and negative predictive value (NPV) of the HS in the diagnosis of BA was 100%, 63.6%, 53.8%, and 100%, respectively. The accuracy was 74.5%. BA patients with non-draining HS had significantly higher levels of gamma-glutamyl transpeptidase (GGTP) than non-BA patients with non-draining HS (p = 0.019) or draining HS (p = 0.0001). CONCLUSIONS: HS plays an important role in the diagnostic strategy of infantile jaundice due to conjugated hyperbilirubinaemia. It is a non-invasive method that only seldomly calls for sedation. A high sensitivity and NPV prevent un-necessary surgery. Because of the low specificity of HS in diagnosing BA, it should be part of a multimodality imaging strategy when the result supports a clinical suspicion of BA. In cases with non-draining HS and normal GGTP blood levels, supplemental imaging modalities are especially needed. FUNDING: none. TRIAL REGISTRATION: not relevant.