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Data about the presentation and the management of primary immune thrombocytopenia (ITP) in very elderly patients (VEPs; aged ≥80 years) are lacking. The aim of the present study was to describe ITP in this subgroup. The data source was the prospective CARMEN-France registry. Patients included between 2013 and 2018 were selected. ITP presentation and management in VEPs was compared to elderly patients (EPs; aged 65-79 years). We assessed factors associated with bleeding at ITP onset in VEPs. Of 541 patients, 184 were included: 87 in the VEP group and 97 in the EP group. The mean age was 85·7 years in the VEP group. Comorbidities were more frequent in the VEP group (67·4% vs. 47·9%). The median platelet count at ITP onset was similar but severe bleeding tended to be more frequent in VEPs (10·3% vs. 4·1%, P = 0·1) as well as mortality. Exposure to ITP drugs, response to first-line treatment, need of second-line treatment, evolution towards persistency, occurrence of bleeding, infection and thrombosis did not differ between groups. In VEPs, factors associated to bleeding were female sex [odds ratio (OR) 4·75, 95% confidence interval (CI) 1·31-17·32] and platelet count of

Objective: To critically evaluate an early childhood caries (ECC) intervention performed by non-dental primary healthcare providers. Methods: This mixed-methods investigation includes data from three sources: (a) a pilot non-randomized controlled trial to examine clinical outcomes at four health centres; (b) stakeholder focus group interviews; and (c) a survey of parents whose children were exposed to the intervention. The pilot study involved four Community Health Centres in rural Cambodia whereby mother-child (6-24 months of age)dyads received oral health education (OHE), toothbrushes, fluoride toothpaste and fluoride varnish on up to six occasions as part of the routine vaccination schedule. Outcomes were as follows: presence of ECC; impacts on oral health-related quality of life (OHRQoL); stakeholder perceptions of intervention delivery; and parental perceptions of fluoride varnish. Results: Participants in the intervention group had six times lower odds of developing ECC than those in the comparison group after controlling for socio-economic status (OR 0.13). Those in the intervention group also had a large reduction OHRQoL scale scores. Key knowledge and practice gaps were identified among stakeholders. Surveyed parents had favourable views of the fluoride varnish placement by medical professionals, and four out of five stated that they would recommend fluoride varnish for other children. Primary healthcare providers, commune council representatives and community health promoters supported oral health interventions being provided in CHCs. Conclusions: OHE and fluoride varnish interventions provided by non-dental primary health workers were feasible and acceptable for stakeholders in a Cambodian setting. The intervention group had lower ECC experience and better OHRQoL at 2 years of age.

Organic acidurias (OAD) and urea-cycle disorders (UCD) are rare inherited disorders affecting amino acid and protein metabolism. As dietary practice varies widely, we assessed their long-term prescribed dietary treatment against published guideline and studied plasma amino acids levels. We analyzed data from the first visit recorded in the European registry and network for intoxication type metabolic diseases (E-IMD, Chafea no. 2010 12 01). In total, 271 methylmalonic aciduria (MMA) and propionic aciduria (PA) and 361 UCD patients were included. Median natural protein prescription was consistent with the recommended daily allowance (RDA), plasma L-valine (57%), and L-isoleucine (55%) levels in MMA and PA lay below reference ranges. Plasma levels were particularly low in patients who received amino acid mixtures (AAMs-OAD) and L-isoleucine:L-leucine:L-valine (BCAA) ratio was 1.0:3.0:3.2. In UCD patients, plasma L-valine, L-isoleucine, and L-leucine levels lay below reference ranges in 18%, 30%, and 31%, respectively. In symptomatic UCD patients who received AAM-UCD, the median natural protein prescription lay below RDA, while their L-valine and L-isoleucine levels and plasma BCAA ratios were comparable to those in patients who did not receive AAM-UCD. Notably, in patients with ornithine transcarbamylase syndrome (OTC-D), carbamylphosphate synthetase 1 syndrome (CPS1-D) and hyperammonemia-hyperornithinemia-homocitrullinemia (HHH) syndrome selective L-citrulline supplementation resulted in higher plasma L-arginine levels than selective L-arginine supplementation. In conclusion, while MMA and PA patients who received AAMs-OAD had very low BCAA levels and disturbed plasma BCAA ratios, AAMs-UCD seemed to help UCD patients obtain normal BCAA levels. In patients with OTC-D, CPS1-D, and HHH syndrome, selective L-citrulline seemed preferable to selective L-arginine supplementation.

BACKGROUND: Pediatric LT are at particular risk of HAT, and its management still constitutes a matter of debate. Our purpose was to study predisposing factors and outcome of HAT post-LT, including the impact of surgical revisions on survival and biliary complications. METHODS: Among 882 primary pediatric LT performed between 1993 and 2015, 36 HAT were encountered (4.1%, 35 fully documented). Each HAT case was retrospectively paired with a LT recipient without HAT, according to diagnosis, age at LT, type of graft, and era. RESULTS: Five-year patient survivals were 77.0% versus 83.9% in HAT and non-HAT paired groups, respectively (P = .321). Corresponding graft survivals were 20.0% versus 80.5% (P < .001), and retransplantation rates 77.7% versus 10.7%, respectively (P < .001). One-year biliary complication-free survivals were 16.6% versus 83.8% in the HAT and non-HAT groups, respectively (P < .001). Regarding chronology of surgical re-exploration, only HAT cases that occurred within 14 days post-LT were re-operated, fourteen of them being explored within 7 days post-LT (revascularization rate: 6/14), versus two beyond 7 days (no revascularization). When revascularization was achieved, graft and biliary complication-free survival rates at 1 year were 33.3% and 22.2%, respectively, both rates being 0.0% in case of failure. CONCLUSIONS: The pejorative prognosis associated with HAT in terms of graft survival is confirmed, whereas patient survival could be preserved through retransplantation. Results suggest that HAT should be re-operated if occurring within 7 days post-LT, but not beyond.

Currently, the only approved hepatitis C virus (HCV) treatment for children aged

The pangenotypic regimen of glecaprevir and pibrentasvir (G/P) is approved to treat adults with chronic hepatitis C virus (HCV) infection, and has yielded high cure rates in adults in clinical trials. Approved treatment options for pediatrics may include ribavirin (RBV). A pangenotypic regimen for pediatric patients remains an unmet need. DORA is an ongoing phase 2/3, non-randomized, open-label study evaluating the pharmacokinetics (PK), safety, and efficacy of G/P in pediatric patients with chronic HCV. This analysis includes Part 1 of the study, conducted in adolescent patients 12-17 years old given the adult regimen of G/P (300 mg/120 mg) once-daily for 8-16 weeks according to the indication durations used in adults. Patients were either treatment-naïve or experienced with interferon (IFN)- based regimens. The primary PK endpoint was steady-state exposures for glecaprevir and pibrentasvir; the primary efficacy endpoint was sustained virologic response 12 weeks post-treatment (SVR12). The secondary efficacy endpoints were on-treatment virologic failure, relapse, and reinfection. Safety and tolerability were monitored. Part 1 enrolled 48 adolescent patients infected with genotypes 1, 2, 3, or 4; 47 of whom were administered G/P. All 47 patients (100%) achieved SVR12. No on-treatment virologic failures or relapses occurred. PK exposures of glecaprevir and pibrentasvir were comparable to exposures in adults. No AEs led to treatment discontinuation, and no serious AEs occurred. CONCLUSION: Adolescent patients with chronic HCV infection treated with G/P achieved a comparable exposure to adults, 100% SVR12 rate, and safety profile consistent with that in adults. This is the first pangenotypic regimen to demonstrate 100% efficacy within the adolescent population in as little as 8 weeks of treatment.

In adults, treatment of hepatitis C virus (HCV) infection with ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (r) with or without dasabuvir (DSV) and ±ribavirin (RBV) results in high rates of sustained virologic response (SVR). However, these regimens have not been investigated in adolescents. This ongoing, open‐label, phase 2/3 study evaluated the pharmacokinetics, safety, and efficacy of OBV/PTV/r+DSV±RBV treatment for 12 weeks in adolescents infected with HCV genotype (GT) 1 without cirrhosis (part 1) and the safety and efficacy of OBV/PTV/r±DSV±RBV treatment for 12 or 24 weeks in adolescents infected with GT1 or GT4 without cirrhosis or with compensated cirrhosis (parts 1 and 2). Patients were 12‐17 years of age and treatment naive or interferon experienced. Treatment regimens were based on HCV GT and cirrhosis status. Endpoints were SVR at posttreatment week 12 (SVR12), adverse events (AEs), and pharmacokinetic parameters. Thirty‐eight adolescents were enrolled, 66% were female patients, and 76% were White; 42%, 40%, and 18% of patients had HCV GT1a, GT1b, and GT4 infections, respectively. Median age was 15 years (range, 12‐17 years), and 1 patient had cirrhosis. The SVR12 rate was 100% (38/38; 95% confidence interval [CI], 90.8%‐100%). No treatment‐emergent grade 3 or 4 laboratory abnormalities were reported. No serious AEs occurred on treatment, and no AEs led to study drug discontinuation. The most common AEs were headache (21%), fatigue (18%), nasopharyngitis (13%), pruritus (13%), and upper respiratory tract infection (11%). Intensive pharmacokinetic results showed OBV, PTV, DSV, and ritonavir drug exposures were comparable to those seen in adults. Conclusion: Treatment with OBV/PTV/r±DSV±RBV was well tolerated and highly efficacious in adolescents with HCV GT1 or GT4 infection.

Chronic hepatitis B virus (HBV) infection and HBV-related hepatitis in children remains an unmet medical need, as current treatments are only partially effective, and only in a limited number of affected children. So-called "immunotolerant" children have not shown increased serological responses to available treatments. In cases involving more active disease, serological response has only been obtained in approximately one-third of patients when using interferon, while other cases exhibited virological response solely under continuous treatment with nucleoside analogs. Guidelines have recently been established to aid pediatricians in effectively managing this condition. With the available medications, no treatment is so far indicated for immunotolerant children, but only for cases presenting increased alanine aminotransferase levels to over 1.5-2 times the upper limit of normal for over 6 months, and without spontaneous HB envelope antigen to antibody seroconversion. The therapeutic arsenal approved by the Food and Drugs Administration and European Medicines Agency for children remains limited because of the lack of large-scale clinical trials validating treatments already approved for the adult population. Yet, the recent discovery of a specific HBV-cell surface receptor, NTCP, allows for new treatment perspectives regarding the future.

Introduction: Vectorcardiographic (VCG) QRS area of left bundle branch block (LBBB) predicts acute hemodynamic response in cardiac resynchronization therapy (CRT) patients. We hypothesized that changes in QRS area occurring with biventricular pacing (BV) might predict acute hemodynamic CRT response (AHR). Methods and Results: VCGs of 624 BV paced electrocardiograms (25 LBBB patients with 35 different pacing configurations) were calculated according to Frank's orthogonal lead system. Maximum QRS vector amplitudes (X-Ampl, Y-Ampl, Z(Ampl), and 3D(Amp)) and QRS areas (X-Area, Y-Area, Z(Area), and 3D(Area)) in the orthogonal leads (X, Y, and Z) and in 3-dimensional projection were measured. Volume of the 3D vector loop and global QRS duration (QRSD) on the surface electrocardiogram were assessed. Differences (Delta) in VCG parameters between BV paced and LBBB QRS complexes were calculated. An increase of 10% in dP/dt max was considered as AHR. LBBB conduction is characterized by a large Z(Area) (109 mu Vs, interquartile range [ IQR]: 75; 135), significantly larger than X-Area (22 mu Vs, IQR: 10; 57) and Y-Area (44 mu Vs, IQR: 32; 62, P< 0.001). Overall, QRS duration, amplitudes, and areas decrease significantly with BV pacing (P

Introduction: Biliary atresia (BA) is the main indication for liver transplantation (LT) in the pediatric age. Donor-selection strategy is still matter of debate. Methods: LT performed at our Institution between 1993-beginning of our living donor program-and 2015 were retrospectively analyzed. Patient and graft survivals were studied in BA patients according to age at LT (before and after 2 years-old) and type of donor (living donor vs deceased donor). Among 609 children, recipients of 649 grafts, the indications for LT were as follows: BA (56.1%), cholestatic diseases (19.4%), liver malignancies (7.5%), fulminant hepatitis (4.3%) and others (12.7%). For BA recipients, 150 DD and 216 LD grafts were used: only primary transplantations (342 grafts) were considered for this study. Results: Overall, the median age at LT was significantly lower for BA patients (median: 1.0 year; range: 0.3-15.7) comparing to other indications (3.9 years; 0.1-22.4) (P < 0.0001). Overall 5-year patient and graft survivals were 86.9% and 82.2% respectively for non-BA, vs 95.1%% and 88.8% for BA patients (P = 0.0001 and P = 0.0033). In the BA subgroup (n = 342 pts), the median age was significantly lower when a LD-LT was performed (0.9 years; 0.4-10.8) comparing to DD-LT (1.4 years; 0.3-15.7) (P < 0.0001). 264 patients have been transplanted < 2 years-old (183 LD and 81 DD) and 78 ≥ 2 years-old (31 LD and 47 DD). Overall re-transplantation rate in BA recipients was 9.3%. 5-year PATIENT survival was comparable for patients transplanted ≥ 2 years-old (97.4%) vs those transplanted < 2 years-old (94.1%) (P = 0.9127); conversely, 5-years GRAFT survival was significantly higher when LT was performed < 2 years-old (90.0% vs 84.1%) (P = 0.0316). In the subgroup of children < 2 years-old, 5-year patient and graft survivals were significantly higher after LD-LT (96.6% and 90.6% respectively), than after DD-LT (88.9% and 81.5%) (P = 0.0156 and P < 0.0001). Conclusions: 1) BA constituted the main indication for LT in children, for whom outcome seems to be better comparing to those transplanted for all other indications; 2) The use of LD-LT allowed to transplant children at a younger age, when compared with DD-LT, with a comparable patient survival rate, but with a better graft survival rate; 3) In the subgroup of BA children transplanted earlier (< 2 years-old), LD-LT provides significantly better outcome in both patient and graft survival rate.

Collaborators :Hörster F, Matzkuhn H, Mütze U, Kowoll ME, Dressel M, Jelsig AM, de Lonlay P, Wijburg FA, Bosch A, Freisinger P, Jeltsch K, Posset R, Boy N, Mengler K, Augoustides-Savvopoulou P, Avram P, Deleanu C, Baumgartner MR, Häberle J, Blasco-Alonso J, Burlina AB, Rubert L, Cazorla AG, Saladelafont ECI, Dionisi-Vici C, Martinelli D, Dobbelaere D, Mention K, Grünewald S, Chakrapani A, Hwu WL, Chien YH, Lee NC, Karall D, Scholl-Bürgi S, Lachmann R, De Laet C, Matsumoto S, de Meirleir L, Mühlhausen C, Schiff M, Peña-Quintana L, Djordjevic M, Sarajlija A, Sykut-Cegielska J, Wisniewska A, Leao-Teles E, Alves S, Vara R, Vives-Pinera I, Ortega DG, Morris A, Zeman J, Honzik T, Chabrol B, Arnaudo F, Cano A, Thompson N, Eyskens F, Lindner M, Lüsebrink N, Jalan A, Sokal E, Legros V, Nassogne MC. INTRODUCTION: Organic acidurias (OAD) and urea-cycle disorders (UCD) are rare inherited disorders affecting amino acid and protein metabolism. As dietary practice varies widely, we assessed their long-term prescribed dietary treatment against published guideline and studied plasma amino acids levels. METHOD: We analyzed data from the first visit recorded in the European registry and network for intoxication type metabolic diseases (E-IMD, Chafea no. 2010 12 01). RESULTS: In total, 271 methylmalonic aciduria (MMA) and propionic aciduria (PA) and 361 UCD patients were included. Median natural protein prescription was consistent with the recommended daily allowance (RDA), plasma L-valine (57%) and L-isoleucine (55%) levels in MMA and PA lay below reference ranges. Plasma levels were particularly low in patients who received amino acid mixtures (AAMs-OAD) and L-isoleucine: L-leucine: L-valine (BCAA) ratio was 1.0:3.0:3.2. In UCD patients, plasma L-valine, L-isoleucine and L-leucine levels lay below reference ranges in 18%, 30% and 31%, respectively. In symptomatic UCD patients who received AAM-UCD, the median natural protein prescription lay below RDA, while their L-valine and L-isoleucine levels and plasma BCAA ratios were comparable to those in patients who did not receive AAM-UCD. Notably, in patients with ornithine transcarbamylase syndrome (OTC-D), carbamylphosphate synthetase 1 syndrome (CPS1-D) and hyperammonemia-hyperornithinemia-homocitrullinemia (HHH) syndrome selective L-citrulline supplementation resulted in higher plasma L-arginine levels than selective L-arginine supplementation. CONCLUSION: While MMA and PA patients who received AAMs-OAD had very low BCAA levels and disturbed plasma BCAA ratios, AAMs-UCD seemed to help UCD patients obtain normal BCAA levels. In patients with OTC-D, CPS1-D and HHH syndrome, selective L-citrulline seemed preferable to selective L-arginine supplementation. This article is protected by copyright. All rights reserved.

Introduction: From 1984 to 2018, 1115 paediatric liver transplantations have been performed, of which 433 with living donors. With patients coming from 13 different countries, our centre has a strong international dimension. The Live Organ Donor Consensus Group has formulated a statement according to which “a psychological evaluation is necessary for each potential donor” [i]. In our centre, we systematically conduct pre-transplant psychological assessments, which consist in a clinical family interview. The complexity of the family situations having increased over the last few years, we aimed to address the relevance and efficiency of our pre-transplant interviews. Methods: Content analysis of 130 pre-transplant reports written between 1/07/2014 and 31/10/2018 were reviewed, as well as personal prospective notes by the psychologist, in the follow-up of the families after transplantation during the same period, with a systemic attention to the transplanted child's family. Results: Our reflective work sheds light on the evolution of our practice of pre-transplant interviews, which has evolved from family interviews focused on the living donor, to interviews that consider all the aspects of the family dynamics, including the cultural dimension. The analysis of our prospective notes revealed that the potential risks are not only related to personal characteristics of the living donor candidate, but can also be connected with his/her environment. Moreover, the psychosocial risk does not concern the donor candidate alone, but may well extend to other significant family members, including those who remained in the country of origin. We are receiving families who have experienced unique life circumstances, such as histories of intra-familial tensions or violence, death of previous children, experiences of war or jail. Family dynamics are affected differently by such circumstances, with psychosocial risks at various level and for different family members as a consequence. As a result of embracing the complexity of such trans-national families, we moved from proceeding to a single family interview focused on the living donor candidate to conducting one or multiple interviews focused on the family situation (including psychiatric or social consultation). Conclusion: In order to prevent short and long-term psychosocial damage for families concerned with living-related donation, we recommend to extend the focus on the donor alone to a focus on the whole family system and history, and to pay attention to the cultural dimension, as this has an impact on important social processes and interactions, which in turn influences the psychological-and sometimes psychiatric-outcomes.

Introduction: From 1984 to 2018, 1115 paediatric liver transplantations (PLTs) have been performed, of which 433 with living donors (LD). In 2000, the Live Organ Donor Consensus Group has formulated a statement according to which “a psychological evaluation is necessary for each potential donor” [i]. Accordingly, we systematically conduct pre-transplant psychological interviews, which consist at least in a clinical family interview. We hypothesize that such approach may predict psychosocial difficulties for families in the course of the transplant. Methods: Content analysis of 130 pre-transplant reports written between 1/07/2014 and 31/10/2018 were reviewed, as well as personal prospective notes by the psychologist, in the follow-up of the families after transplantation during the same period, together with interviews with the co-ordinator of the transplant program, the surgeon, and the chief nurse, to triangulate the data from our own personal notes. Results: The results hereafter are based on the systematic analysis of the first 54 situations of living donor paediatric transplantation. After transplantation, 39/54 (72%) families did not experience particular psychosocial difficulties whereas 15 (28%) needed psychosocial support. Only 9 of these 15 situations had been identified as being at risk, through our clinical interview before transplantation. The red flags identified by the psychologist in relation to these families were in adequacy with the type of difficulties experienced after transplantation, such as tensions within the parental couple, psychosocial fragility of one parent, and previous death of children. Looking at the remaining 6 (11%) whose psychosocial risk had not been identified we analysed whether it would have been possible to predict post-operative psychosocial events or adjustments, based on our pre-transplant psychological assessment. In 3 situations, medical complications and a long hospitalization were the main determinant of the subsequent psychosocial difficulties, which were therefore not predictable. In 3 situations however, the risk might have been predicted if we had investigated more in-depth the larger environment and history of the family, for instance a previous loss of a child in one family, a history of long period of mother-child separation in another, and a complex relationship between a donor candidate and his recent girlfriend. Conclusion: Our results based on the systematic analysis of 54 psychological pre-transplant reports suggests that a systemic approach with at least a clinical family interview predicts in 48/54 (89%) psychosocial risks and points of attention for living donor candidates and their family before paediatric liver transplantation. In the 6/54 (11%) remaining situations, we hypothesize that a more in-depth systemic approach may improve our prediction of psychosocial difficulties.

The development of liver cell transplantation (LCT), considered a major biotechnological breakthrough, was intended to provide more accessible treatments for liver disease patients. By preserving the native recipient liver and decreasing hospitalization time, this innovative approach has progressively gained interest among clinicians. LCT initially targets inborn errors of liver metabolism, enabling the compensation of deficient metabolic functions for up to 18 months post-transplantation, supporting its use at least as a bridge to transplantation. The rigorous clinical development and widespread use of LCT depends strongly on controlled and consistent clinical trial data, which may help improve several critical factors, including the standardization of raw biological material and immunosuppression regimens. Substantial effort has also been made in defining and optimizing the most efficient cell population to be transplanted in the liver setting. Although isolated hepatocytes remain the best cell type, showing positive clinical results, their widespread use is hampered by their poor resistance to both cryopreservation and in vitro culture, as well as ever-more-significant donor shortages. Hence, there is considerable interest in developing more standardized and widely accessible cell medicinal products to improve engraftment permanency and post-cell transplantation metabolic effects. Significance In this therapeutic approach to liver disease, new solutions are being designed and evaluated to bypass the documented limitations and move forward toward wide clinical use. Future developments also require a deep knowledge of regulatory framework to launch specific clinical trials that will allow clear assessment of cell therapy and help patients with significant unmet medical needs.

SummaryAims The aim of this study was to evaluate the usability and safety of the Explorer Endoscopy Mask® (EM) as an alternative to endotracheal intubation in children undergoing elective esogastroduodenoscopy (EGD) under general anesthesia (GA). Methods This study was a retrospective observational study. The study was undertaken at the pediatric digestive endoscopy suite in the Cliniques universitaires Saint-Luc, Brussels, Belgium. We retrospectively analyzed the occurrence of minor and major airway-related adverse effects during pediatric EGD procedures performed under GA with the EM between June 2014 and March 2015. Results During the study period, 173 patients underwent EGD. Their mean age was 8.4 years (median: 9.1 years, range 4 months to 16 years). Mean duration of endoscopy (from insertion to removal of the endoscope) was 12.6 min (median: 12 min, range 3–47 min). The use of EM was uneventful in 159 (92%) cases. There were 24 airway-related adverse events in 14 children. Hypoxemia (SpO2

Background: Ophthalmic abnormalities are amongst the 5 major criteria for diagnosing autosomal dominant Alagille Syndrome (AS). Embryotoxon, pseudo-papilledema and pigmentary retinopathy being most frequently part of the syndrome. Papilledema with or without intracranial hypertension (ICHT) are rarely described. We report 9 cases of bilateral papilloedema, 4 associated to ICHT at lumbar puncture (LP) , all being diagnosed idiopathic ICHT in children with AS. Methods: We reviewed ophthalmologic examination data from 85 pediatric patients with clinically (n=48) and/or genetically (n=37) proven AS followed in two referring hospitals (UCL St Luc Brussels, n=75; HUG Geneva n=10). Patients were included if data were available before and after liver transplantation (LT). Results: 69 patients fulfilled inclusions criteria. 41 patients (41/69, 59%) of this group had LT of whom 2 developed true papilloedema before LT and 6 after LT (6/41, 14%). One papilloedema, but with normal neurologic exam and a rapid resolution was found in a non-transplanted child (1/28, 3%). Papilloedema resolved spontaneously in 4 patients (2 with pre-transplant onset) (4/69, 6%). In a fifth patient, severe papilloedema without documented ICHT (normal LP) resolved after switching tacrolimus to cyclosporine and adding acetazolamide. In only 4 remaining patients; the ICHT was revealed at LP. In all patients normal neurological exam and cerebral MRI were reported (4/69, 6%). ICHT was treated by steroids alone in one patient, and in the 3 others patients in combination with acetazolamide and a switch from tacrolimus to cyclosporine. Among these 3 patients, ventriculo-peritoneal derivation was ultimately required in 2 for severe progressive visual loss. We detected pseudo-papilloedema in 7 additional children (7/69, 10%); which was persistent and unchanged after LT in n=4. Conclusion: Besides pseudopapilloedema, true papilloedema with or without proven ICHT in a context of AS occurs in probably more patients than expected. A close follow-up of ophthalmologic complications should be implemented for these patients before and/or after LT because the risk of severe and irreversible visual loss.

Background: Concomitant presence of autoimmune hepatitis and primary sclerosing cholangitis (PSC) is labelled as autoimmune sclerosing cholangitis (ASC) in children. Based upon the possible implication of microbiota and microbial metabolites, such as bile acids (BAs), in the pathogenesis of PSC, oral antibiotics are increasingly being used as a novel therapeutic approach and shown to have benefit in PSC but their role in pediatric ASC is not well evaluated. We prospectively analysed the gut microflora and serum BAs pool before and after antibiotic therapy in children with ASC or PSC alone, and evaluated whether changes in gut microflora and/or BAs correlated with response to treatment. Methods: Patients diagnosed with ASC or PSC on basis of biochemical, liver biopsy and radiology findings were included. They prospectively received metronidazole (MTZ) for 14 days as induction or rescue therapy. MTZ were administrated in addition to the standard treatment of UDCA for PSC patients and azathioprine, and UDCA and/or steroids for ASC patients. Stool and serum samples were collected before and after MTZ therapy. DNA isolation, amplification and Illumina sequencing to profile the microbiota composition were performed using the bacterial 16s rRNA while serum BAs were assessed by ultraperformance liquid chromatography coupled to mass spectrometry. The beta-diversity measured the dissimilarity between each paired stool samples. The outcome parameters to assess the efficacy of antibiotics were reduction liver enzymes and subsequently achievement of sustained biochemical remission. Results: Seven children (4 ASC, 3 PSC) were included, of which 5 have a concomitant ulcerative colitis (UC). All patients showed a significant decrease in their AST (-55%, p< 0.025), ALT (-56%, p< 0.025) and GGT (-41%, p< 0.025) under MTZ. Three children relapsed after stopping MTZ while the four others children showed a sustained biochemical remission (liver enzymes below 1.5 times upper limit of normal) after a median follow-up of 375 days. Among these four patients, three exhibited a wide different microbial composition before and after MTZ as expressed by the betadiversity variation. They also expanded their total serum BAs size (from 1542.96 to 2620.99 pmol/100μl, +69.87%), primarily due to the large increment of UDCA and its glycineand taurine-conjugates which finally represented more than half of the total serum BAs. On the contrary, the microbiota of patients who relapsed remained unchanged pre-and post MTZ and total BAs pool decreased. Conclusion: Our study suggests that oral antibiotic could be an effective treatment of ASC and PSC, especially those with a concomitant UC, and that intestinal microflora and BAs play a major role in these diseases as sustained biochemical remission is associated with wide changes in gut microbiota communities and BAs profile after taking antibiotics.

The scientific career of eminent experimentalist and psychological tester James McKeen Cattell (1860-1944) began at the Johns Hopkins University during the year (1882-1883) he held the university's Fellowship in Philosophy. This article opens by sketching the scope of Cattell's lifetime achievement and then briefly reviews the historical attention that his life and career has attracted during the past few decades. It then outlines the origins and evolution of Cattell's "scientific ideology," traces the course of events that led to his fellowship, reviews his earliest studies at Johns Hopkins, and analyzes in some detail his initial laboratory successes. These laid the groundwork for his later distinguished work as a psychological experimentalist, both in Europe and America. It concludes, however, that even as Cattell's early experimental achievements impressed others, the personal arrogance he exhibited during his year in Baltimore served to alienate him from his colleagues and teachers. Over the long run, this arrogance and his often-antagonistic approach to others continued to color (and even shape) his otherwise distinguished more than 50-year scientific career.

Inclusion in Canadian schools, both academic and social, is explored through the historic legislative structures that have resulted in a diversity of approaches to meeting the educational needs of Canadians. Innovative programmes that have been developed which showcase Canadian commitment to inclusive academic and social practices are described. Finally, we explore some of the challenges that Canadians are facing in truly being inclusive in our educational practices, and we make three specific recommendations about how we can become more inclusive. [ABSTRACT FROM AUTHOR]

Background The prognostic impact of improvement in health-related quality of life (QoL) and its relation to response in cardiac resynchronization therapy (CRT) recipients remains unknown. Aim To assess the correspondence between response to CRT and improvements in QoL and to verify if a change in QoL after pacing influences outcome in CRT patients. Methods Ninety-seven participants of the Triple-Site Versus Standard Cardiac Resynchronization Therapy Trial (TRUST CRT) randomized trial, in New York Heart Association class III-IV, QRS width ≥ 120 ms, left ventricular ejection fraction ≤35%, and significant mechanical dyssynchrony were included. Subjects filled out the Minnesota-QoL questionnaire prior to and 6 months after CRT with defibrillator (CRT-D) implantation. Data on major adverse cardiac events (MACEs: death, heart failure hospitalization, heart transplant) collected within the next 2.5 years and adjudicated blindly constituted the censoring variables. Results Within the first 6 months of resynchronization QoL improved in 81%, while worsening in 19% of patients. Clinical response, but not the echocardiographic one, was associated with improved QoL. During subsequent 2.5 years MACEs occurred in 37% of patients (23% died). Subjects without QoL improvement were significantly (both P < 0.05) more prone to experience MACE (61% vs 32%) and die (44% vs 18%) within the follow-up. Unimproved QoL increased the probability of future MACE by 2.7 times (95% confidence intervals [CI]: 1.26–5.83; P = 0.01) and death by 3.2 times (95% CI: 1.23–8.32; P = 0.02) independently from clinical and echocardiographic response. Conclusions Clinical response, but not the echocardiographic one, was associated with improved QoL in CRT recipients. These preliminary data suggest that lack of improvement in QoL after CRT was associated with a strongly unfavorable prognosis, regardless of functional or echocardiographic response. Our results merit further studies with a larger number of patients.

The microsomal protein per gram of liver (MPPGL) is an important scaling factor in the in vitro-in vivo extrapolation of metabolic data obtained in liver microsomes. This study aimed to determine the MPPGL in four biliary atresia patients (0.6-1.6 years old) undergoing liver transplantation, as it is known that the MPPGL is affected by age and possibly by liver disease. Due to the presence of bilirubin in the homogenates and microsomes, the NADPH-cytochrome reductase activity was used to determine the recovery factor, rather than methods using the dithionite difference spectrum. A mean value of 18.73 (± 2.82) mg/g (geometric mean ± SD, n = 4) was observed, which is lower than the expected MPPGL based on the age of the patients (26.60 ± 0.40 mg/g). This suggests a decreased amount of microsomal protein in the livers of biliary atresia patients. Moreover, no differences in MPPGL between different zones of the liver could be detected. Copyright

Background The aim of this study was to assess sex differences in major congenital anomaly (CA) diagnoses within a national population sample; to examine the influence of sociodemographic and maternal factors on these risks; and to conduct a meta-analysis using estimates from other population-based studies. Methods We conducted a population-based study in a United Kingdom research database of prospectively collected primary care data (The Health Improvement Network) including children born 1990 to 2009 (n = 794,169) and identified major CA diagnoses using EUROCAT (European Surveillance of Congenital Anomalies) classification. Prevalence ratios (PR) were used to estimate the risk of CA in males compared with females for any CA, system-specific subgroups and specific CA diagnoses. In a subpopulation of children whose medical records were linked to their mothers', we assessed the effect of adjusting for sociodemographic and maternal factors on sex odds ratios. PRs were pooled with measures from previously published studies. Results The prevalence of any CA was 307/10,000 in males (95% CI, 302–313) and 243/10,000 in females (95% CI, 238–248). Overall the risk of any CA was 26% greater in males (PR (male: female) 1.26, 95% CI, 1.23–1.30) however there was considerable variation across specific diagnoses. The magnitude and direction of risk did not change for any specific CA upon adjustment for sociodemographic and maternal factors. Our PRs were highly consistent with those from previous studies. Conclusion The overall risk of CA is greater in males than females, although this masked substantial variation by specific diagnoses. Sociodemographic and maternal factors do not appear to affect these risks. Birth Defects Research (Part A) 100:79–91, 2014. © 2014 Wiley Periodicals, Inc.