Clinical, biochemical, and molecular overview of transaldolase deficiency and evaluation of the endocrine function: Update of 34 patients.

BACKGROUND: Transaldolase deficiency (TALDO-D) is a rare autosomal recessive inborn error of the pentose phosphate pathway. Since its first description in 2001, several case reports have been published, but there has been no comprehensive overview of phenotype, genotype, and phenotype-genotype correlation. METHODS: We performed a retrospective questionnaire and literature study of clinical, biochemical, and molecular data of 34 patients from 25 families with proven TALDO-D. In some patients, endocrine abnormalities have been found. To further evaluate these abnormalities, we performed biochemical investigations on blood of 14 patients. RESULTS AND CONCLUSIONS: Most patients (n = 22) had an early-onset presentation (prenatally or before 1 month of age); 12 patients had a late-onset presentation (3 months to 9 years). Main presenting symptoms were intrauterine growth restriction, dysmorphic facial features, congenital heart disease, anemia, thrombocytopenia, and hepato(spleno)megaly. An older sib of two affected patients was asymptomatic until the age of 9 years, and only after molecular diagnosis was hepatomegaly noted. In some patients, there was gonadal dysfunction with low levels of testosterone and secondary luteinizing hormone (LH) and follicle-stimulating hormone (FSH) abnormalities later in life. This overview provides information that can be helpful for managing patients and counseling families regarding prognosis. Diagnostic guidelines, possible genotype-phenotype correlations, treatment options, and pathophysiological disease mechanisms are proposed.

Healthcare transition in pediatric liver transplantation: The perspectives of pediatric and adult healthcare professionals.

INTRODUCTION: Transition from pediatric to adult services of young people with a liver transplant is an important priority due to increasing numbers of young people surviving into adulthood. There is increased incidence of graft loss and non-adherence following transfer to adult services. Although studies have considered the views and perceptions of young people who have undergone liver transplantation and their parents about transition, there is currently no qualitative research with healthcare professionals working in the field of liver transplantation. The aim of this study was to elicit the views of this group of stakeholders about barriers and facilitators of an effective transition process. METHODS: Semi-structured interviews were carried out with 11 HCPs from pediatric and adult liver transplant programs and from a range of professional backgrounds. Interviews were transcribed verbatim and analyzed using thematic analysis. RESULTS: Four themes were identified: "non-adherence and psychosocial issues," "need for better psychological support," "the role of parents," and "the emotional impact of transition on healthcare professionals." Within these themes, professionals described factors which hindered or promoted an effective transition process. CONCLUSIONS: Screening tools which address psychological and social aspects of the lives of young people should be used in routine practice to identify patients requiring psychosocial support and to identify those at risk of non-adherence. All staff involved with transition should be trained in the use of psychosocial screening strategies. The development of a formal referral pathway so that young people can access psychological support in adult services is recommended.

SCYL1 variants cause a syndrome with low γ-glutamyl-transferase cholestasis, acute liver failure, and neurodegeneration (CALFAN).

PURPOSE: Biallelic mutations in SCYL1 were recently identified as causing a syndromal disorder characterized by peripheral neuropathy, cerebellar atrophy, ataxia, and recurrent episodes of liver failure. The occurrence of SCYL1 deficiency among patients with previously undetermined infantile cholestasis or acute liver failure has not been studied; furthermore, little is known regarding the hepatic phenotype. METHODS: We aimed to identify patients with SCYL1 variants within an exome-sequencing study of individuals with infantile cholestasis or acute liver failure of unknown etiology. Deep clinical and biochemical phenotyping plus analysis of liver biopsies and functional studies on fibroblasts were performed. RESULTS: Seven patients from five families with biallelic SCYL1 variants were identified. The main clinical phenotype was recurrent low γ-glutamyl-transferase (GGT) cholestasis or acute liver failure with onset in infancy and a variable neurological phenotype of later onset (CALFAN syndrome). Liver crises were triggered by febrile infections and were transient, but fibrosis developed. Functional studies emphasize that SCYL1 deficiency is linked to impaired intracellular trafficking. CONCLUSION: SCYL1 deficiency can cause recurrent low-GGT cholestatic liver dysfunction in conjunction with a variable neurological phenotype. Like NBAS deficiency, it is a member of the emerging group of congenital disorders of intracellular trafficking causing hepatopathy.

Progressive deafness-dystonia due to SERAC1 mutations: A study of 67 cases.

OBJECTIVE: 3-Methylglutaconic aciduria, dystonia-deafness, hepatopathy, encephalopathy, Leigh-like syndrome (MEGDHEL) syndrome is caused by biallelic variants in SERAC1. METHODS: This multicenter study addressed the course of disease for each organ system. Metabolic, neuroradiological, and genetic findings are reported. RESULTS: Sixty-seven individuals (39 previously unreported) from 59 families were included (age range = 5 days-33.4 years, median age = 9 years). A total of 41 different SERAC1 variants were identified, including 20 that have not been reported before. With the exception of 2 families with a milder phenotype, all affected individuals showed a strikingly homogeneous phenotype and time course. Severe, reversible neonatal liver dysfunction and hypoglycemia were seen in >40% of all cases. Starting at a median age of 6 months, muscular hypotonia (91%) was seen, followed by progressive spasticity (82%, median onset = 15 months) and dystonia (82%, 18 months). The majority of affected individuals never learned to walk (68%). Seventy-nine percent suffered hearing loss, 58% never learned to speak, and nearly all had significant intellectual disability (88%). Magnetic resonance imaging features were accordingly homogenous, with bilateral basal ganglia involvement (98%); the characteristic "putaminal eye" was seen in 53%. The urinary marker 3-methylglutaconic aciduria was present in virtually all patients (98%). Supportive treatment focused on spasticity and drooling, and was effective in the individuals treated; hearing aids or cochlear implants did not improve communication skills. INTERPRETATION: MEGDHEL syndrome is a progressive deafness-dystonia syndrome with frequent and reversible neonatal liver involvement and a strikingly homogenous course of disease. Ann Neurol 2017;82:1004-1015.

The Experiences of Young Liver Patients Transferring From Children's to Adult Services and Their Support Needs for a Successful Transition.

BACKGROUND: The period of transition from pediatric to adult services represents a time when young people need support, information, and appropriate care in order to successfully move. It is a period that is associated with nonadherence and disengagement with care. OBJECTIVE: To explore the experiences of young liver transplant recipients transitioning to adult services and determine what they require in order to achieve a successful move. The research also explored the possibility of using a mobile phone application (app) as a tool to support transition. DESIGN: Qualitative approach using novel arts-based focus groups and one-to-one interviews. PARTICIPANTS: Twenty-one young people aged 16 to 25 years, 16 health-care professionals involved in their care, and 7 young people as follow-up. Participants used services provided by the 3 liver centers in England (Leeds, Birmingham, and London). RESULTS: Data highlighted the variability of transition pathways in England for young people moving from child to adult health services. The results showed that they required clear information regarding transition processes including specific medical information and that there was a shortfall in such information. Support was required in the form of a designated transition coordinator or similar specialist who could act as a point of reference and guidance throughout the process. Transitions needed to be individualized and based upon transition readiness rather than age, although the research showed that age cut-offs were still used. CONCLUSION: Young people welcomed apps to provide information, reminders, contacts, and connections. Future research should explore the efficacy of such apps.

Liver Failure in Early Infancy: Aetiology, Presentation, and Outcome.

OBJECTIVE: Acute liver failure (ALF) in early infancy is rare and challenging to recognize and manage. We aim to describe the presentation and outcome of infants with ALF according to their final aetiology to elucidate features to facilitate early recognition leading to prompt diagnosis and management. METHODS: All infants presenting within 120 days from birth with liver failure were included in a retrospective review over a 19-year period. The aetiology, clinical features, presenting investigations, and outcome were collected. RESULTS: Seventy-eight young infants presented with ALF. The aetiology was established in 94% and included metabolic disease (36%), hypoxic-ischaemic (HI) insult (19%), infection (17%), neonatal haemochromatosis (9%), and infiltrative disease (9%). Infections, infiltrative disease, and acute HI insult usually resulted in higher transaminases and international normalized ratio, whereas neonatal haemochromatosis and tyrosinaemia were characterized by lower or near normal transaminases. Overall jaundice was not visible in 24% of infants at presentation. Forty-five (58%) infants were alive at discharge from hospital. Survival at 1 year was 53% and survival with native liver 50%. Later deaths occurred in infants with mitochondrial disease. Six infants received a liver transplant and 4 subsequently died from their underlying disease. CONCLUSION: ALF should be considered in any young infant with a coagulopathy as transaminases and/or bilirubin levels can be near normal at presentation. Better intensive care and the judicious use of liver transplantation may have contributed to the improved outcomes for this group compared with previous decades.

Using Mobile Phone Technology to Support Young Liver Transplant Recipients Moving to Adult Services.

BACKGROUND: The process and preparation of moving from child to adult services (transition) is a challenging period of time for young people and represents significant changes in care and support systems. The proliferation of mobile phone applications for health purposes suggests that it is an area for further investigation. OBJECTIVE: The review explores the potential to use mobile phone technology to help support young liver transplant recipients moving to adult services. It represents the first review conducted in this specialism and considers a new model of support for young liver patients. METHODS: A systematic rapid review of the published peer-reviewed literature. RESULTS: Two searches were conducted: Search 1: the use of technology to support transition to adult services (6 studies) and Search 2: how best to support liver transplant recipients during transition (6 studies). DISCUSSION: Research shows that to achieve positive transition young people need information about their condition and transition. The process needs to be guided by transition readiness, rather than the young persons' age. Although parents and support networks should be in place and are valued, transition should build upon self-management and independence. Results suggest that there appears to be scope to use mobile phone technology to support transition. This is the first time a review has explored the types of issues or concerns facing liver transplant patients and how these can be addressed through mobile phone technology.

Liver disease in infancy caused by oxysterol 7 α-hydroxylase deficiency: successful treatment with chenodeoxycholic acid.

A child of consanguineous parents of Pakistani origin developed jaundice at 5 weeks and then, at 3 months, irritability, a prolonged prothrombin time, a low albumin, and episodes of hypoglycaemia. Investigation showed an elevated alanine aminotransferase with a normal γ-glutamyl-transpeptidase. Analysis of urine by electrospray ionisation tandem mass spectrometry (ESI-MS/MS) showed that the major peaks were m/z 480 (taurine-conjugated 3ß-hydroxy-5-cholenoic acid) and m/z 453 (sulphated 3ß-hydroxy-5-cholenoic acid). Analysis of plasma by gas chromatography-mass spectrometry (GC-MS) showed increased concentrations of 3ß-hydroxy-5-cholenoic acid, 3ß-hydroxy-5-cholestenoic acid and 27-hydroxycholesterol, indicating oxysterol 7 α-hydroxylase deficiency. The patient was homozygous for a mutation (c.1249C>T) in CYP7B1 that alters a highly conserved residue in oxysterol 7 α-hydroxylase (p.R417C) - previously reported in a family with hereditary spastic paraplegia type 5. On treatment with ursodeoxycholic acid (UDCA), his condition was worsening, but on chenodeoxycholic acid (CDCA), 15 mg/kg/d, he improved rapidly. A biopsy (after 2 weeks on CDCA), showed a giant cell hepatitis, an evolving micronodular cirrhosis, and steatosis. The improvement in liver function on CDCA was associated with a drop in the plasma concentrations and urinary excretions of the 3ß-hydroxy-Δ5 bile acids which are considered hepatotoxic. At age 5 years (on CDCA, 6 mg/kg/d), he was thriving with normal liver function. Neurological development was normal apart from a tendency to trip. Examination revealed pes cavus but no upper motor neuron signs. The findings in this case suggest that CDCA can reduce the activity of cholesterol 27-hydroxylase - the first step in the acidic pathway for bile acid synthesis.

Mutations in VPS33B, encoding a regulator of SNARE-dependent membrane fusion, cause arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome.

ARC syndrome (OMIM 208085) is an autosomal recessive multisystem disorder characterized by neurogenic arthrogryposis multiplex congenita, renal tubular dysfunction and neonatal cholestasis with bile duct hypoplasia and low gamma glutamyl transpeptidase (gGT) activity. Platelet dysfunction is common. Affected infants do not thrive and usually die in the first year of life. To elucidate the molecular basis of ARC, we mapped the disease to a 7-cM interval on 15q26.1 and then identified germline mutations in the gene VPS33B in 14 kindreds with ARC. VPS33B encodes a homolog of the class C yeast vacuolar protein sorting gene, Vps33, that contains a Sec1-like domain important in the regulation of vesicle-to-target SNARE complex formation and subsequent membrane fusion.

Bile acid-CoA ligase deficiency--a new inborn error of bile acid metabolism.

Born at 27 weeks gestation, a child of consanguineous parents of Pakistani origin required prolonged parenteral nutrition. She developed jaundice, with extensive fibrosis and architectural distortion at liver biopsy; jaundice resolved with supportive care. Serum γ-glutamyl transpeptidase values were within normal ranges. The bile acids in her plasma and urine were >85% unconjugated (non-amidated). Two genes encoding bile-acid amidation enzymes were sequenced. No mutations were found in BAAT, encoding bile acid-CoA : aminoacid N-acyl transferase. The patient was homozygous for the missense mutation c.1012C > T in SLC27A5, predicted to alter a highly conserved amino-acid residue (p.H338Y) in bile acid-CoA ligase (BACL). She also was homozygous for the missense mutation c.1772A > G in ABCB11, predicted to alter a highly conserved amino-acid residue (p.N591S) in bile salt export pump (BSEP). BACL is essential for reconjugation of bile acids deconjugated by gut bacteria, and BSEP is essential for hepatocyte-canaliculus export of conjugated bile acids. A female sibling born at term had the same bile-acid phenotype and SLC27A5 genotype, without clinical liver disease. She was heterozygous for the c.1772A > G ABCB11 mutation. This is the first report of a mutation in SLC27A5. The amidation defect may have contributed to cholestatic liver disease in the setting of prematurity, parenteral nutrition, and homozygosity for an ABCB11 mutation.

Differences in presentation and progression between severe FIC1 and BSEP deficiencies.

BACKGROUND & AIMS: Progressive familial intrahepatic cholestasis (PFIC) with normal serum levels of gamma-glutamyltranspeptidase can result from mutations in ATP8B1 (encoding familial intrahepatic cholestasis 1 [FIC1]) or ABCB11 (encoding bile salt export pump [BSEP]). We evaluated clinical and laboratory features of disease in patients diagnosed with PFIC, who carried mutations in ATP8B1 (FIC1 deficiency) or ABCB11 (BSEP deficiency). Our goal was to identify features that distinguish presentation and course of these two disorders, thus facilitating diagnosis and elucidating the differing consequences of ATP8B1 and ABCB11 mutations. METHODS: A retrospective multi-center study was conducted, using questionnaires and chart review. Available clinical and biochemical data from 145 PFIC patients with mutations in either ATP8B1 (61 "FIC1 patients") or ABCB11 (84 "BSEP patients") were evaluated. RESULTS: At presentation, serum aminotransferase and bile salt levels were higher in BSEP patients; serum alkaline phosphatase values were higher, and serum albumin values were lower, in FIC1 patients. Elevated white blood cell counts, and giant or multinucleate cells at liver biopsy, were more common in BSEP patients. BSEP patients more often had gallstones and portal hypertension. Diarrhea, pancreatic disease, rickets, pneumonia, abnormal sweat tests, hearing impairment, and poor growth were more common in FIC1 patients. Among BSEP patients, the course of disease was less rapidly progressive in patients bearing the D482G mutation. CONCLUSIONS: Severe forms of FIC1 and BSEP deficiency differed. BSEP patients manifested more severe hepatobiliary disease, while FIC1 patients showed greater evidence of extrahepatic disease.

Severe bile salt export pump deficiency: 82 different ABCB11 mutations in 109 families.

BACKGROUND & AIMS: Patients with severe bile salt export pump (BSEP) deficiency present as infants with progressive cholestatic liver disease. We characterized mutations of ABCB11 (encoding BSEP) in such patients and correlated genotypes with residual protein detection and risk of malignancy. METHODS: Patients with intrahepatic cholestasis suggestive of BSEP deficiency were investigated by single-strand conformation polymorphism analysis and sequencing of ABCB11. Genotypes sorted by likely phenotypic severity were correlated with data on BSEP immunohistochemistry and clinical outcome. RESULTS: Eighty-two different mutations (52 novel) were identified in 109 families (9 nonsense mutations, 10 small insertions and deletions, 15 splice-site changes, 3 whole-gene deletions, 45 missense changes). In 7 families, only a single heterozygous mutation was identified despite complete sequence analysis. Thirty-two percent of mutations occurred in >1 family, with E297G and/or D482G present in 58% of European families (52/89). On immunohistochemical analysis (88 patients), 93% had abnormal or absent BSEP staining. Expression varied most for E297G and D482G, with some BSEP detected in 45% of patients (19/42) with these mutations. Hepatocellular carcinoma or cholangiocarcinoma developed in 15% of patients (19/128). Two protein-truncating mutations conferred particular risk; 38% (8/21) of such patients developed malignancy versus 10% (11/107) with potentially less severe genotypes (relative risk, 3.7 [confidence limits, 1.7-8.1; P = .003]). CONCLUSIONS: With this study, >100 ABCB11 mutations are now identified. Immunohistochemically detectable BSEP is typically absent, or much reduced, in severe disease. BSEP deficiency confers risk of hepatobiliary malignancy. Close surveillance of BSEP-deficient patients retaining their native liver, particularly those carrying 2 null mutations, is essential.

Renal function evaluated by measured GFR during follow-up in pediatric liver transplant recipients.

Calcineurin inhibitors form the mainstay of immunosuppression in pediatric liver transplantation, but may cause significant nephrotoxicity. We evaluated renal function in liver transplant recipients treated with a tacrolimus-based immunosuppressive regimen. GFR was measured using 99 mTc-DTPA in patients pretransplant and annually thereafter. GFR calculated by Schwartz formula was compared with the measured values. Sixty patients who underwent 69 transplants were followed for at least one yr post-transplant (median three yr). In children over two yr of age at transplant GFR fell significantly from pretransplant (140 mL/min/1.73 m(2)) to one yr post-transplant (112 mL/min/1.73 m(2)) (p = 0.01) but thereafter there was no significant decline. In younger children the picture was confounded by maturation of renal function, but again there was no significant fall to five yr post-transplant. Although 13 (22%) patients developed renal dysfunction post-transplant, none required renal replacement therapy. cGFR correlated poorly with measured values (r = 0.21). Use of a tacrolimus-based immunosuppressive regimen is associated with an initial decline in GFR, though this picture is confounded in younger children by normal maturation of renal function. There is no further significant fall in GFR in the medium-term. The Schwartz formula is inaccurate in determining GFR in this patient group.

Randomized, double-blind, placebo-controlled trial of corticosteroids after Kasai portoenterostomy for biliary atresia.

UNLABELLED: The objective of this study was to evaluate adjuvant corticosteroids after Kasai portoenterostomy for biliary atresia. The study consisted of a prospective, 2-center, double-blind, randomized, placebo-controlled trial of post-Kasai portoenterostomy corticosteroids (oral prednisolone: 2 mg/kg/day from day 7 to day 21 and 1 mg/kg/day from day 22 to day 28). The data were compared with chi2 or Mann-Whitney tests, as appropriate. Seventy-one postoperative infants with type 3 biliary atresia were randomized to receive either oral prednisolone (n = 36) or a placebo (n = 37). At 1 month, the median bilirubin level was lower in the steroid group (66 versus 92 micromol/L, P = 0.06), but no difference was evident at 6 (P = 0.56) or 12 (P = 0.3) months. The proportion of infants with a normal bilirubin level (<20 micromol/L) at 6 (47% versus 49%, P = 0.89) and 12 months (50% versus 40%, P = 0.35) was not significantly different. The need for transplantation by 6 (12% versus 13%, P = 0.99) and 12 months (26% versus 35%, P = 0.47) was not significantly different. The steroid effect was more pronounced in younger infants (less than 70 days at Kasai portoenterostomy, n = 51), with a reduced bilirubin level at 1 month (64 versus 117 micromol/L, P = 0.01) and with a greater proportion with a normal bilirubin level at 12 months (54% versus 37%, P = 0.22). CONCLUSION: There was a beneficial effect on the rate of reduction of bilirubin in the early postoperative period (specifically in infants less than 70 days old at surgery), but this steroid regimen did not reduce the need for liver transplantation.

Outcomes of Percutaneous Portal Vein Intervention in a Single UK Paediatric Liver Transplantation Programme.

INTRODUCTION: Percutaneous transluminal angioplasty (PTA), with or without stent placement, has become the treatment of choice for portal vein complications (PVC) following liver transplantation. We aimed to assess long-term outcomes of intervention in paediatric transplant recipients, in a single institution. MATERIALS AND METHODS: 227 children received 255 transplants between November 2000 and September 2016. 30 patients developed PVC of whom 21 had percutaneous intervention. Retrospective clinical and procedural outcome data on these 21 patients were collected. RESULTS: 21 patients, with median age 1.7 years (range 0.4-16.2), underwent 42 procedures with PTA with or without stenting. 36 procedures were for PV stenosis and 6 for PV thrombosis. Treatment was with primary PTA, with stenting reserved for suboptimal PTA result or restenosis within 3 months. 28 procedures were performed with PTA and 13 with stenting. Technical success (>50% reduction in mean pressure gradient, absolute pressure gradient ≤4 mmHg or venographic stenosis <30%) was achieved in 41 procedures. Failure to recanalise a thrombosed PV occurred in 1 procedure. There were no major procedural complications. Patients were followed-up with serial Doppler ultrasound surveillance. Kaplan-Meier estimated median primary patency was 9.9 months, with primary-assisted patency of 95% after median follow-up of 45.5 months (range 11.1-171.6). CONCLUSION: With regular surveillance, excellent patency rates can be achieved following percutaneous intervention for PVC post-paediatric liver transplantation.

Outcomes of surgical management of familial intrahepatic cholestasis 1 and bile salt export protein deficiencies.

Progressive familial intrahepatic cholestasis (PFIC) with normal circulating gamma-glutamyl transpeptidase levels can result from mutations in the ATP8B1 gene (encoding familial intrahepatic cholestasis 1 [FIC1] deficiency) or the ABCB11 gene (bile salt export protein [BSEP] deficiency). We investigated the outcomes of partial external biliary diversion, ileal exclusion, and liver transplantation in these two conditions. We conducted a retrospective multicenter study of 42 patients with FIC1 deficiency (FIC1 patients) and 60 patients with BSEP deficiency (BSEP patients) who had undergone one or more surgical procedures (57 diversions, 6 exclusions, and 57 transplants). For surgeries performed prior to transplantation, BSEP patients were divided into two groups, BSEP-common (bearing common missense mutations D482G or E297G, with likely residual function) and BSEP-other. We evaluated clinical and biochemical outcomes in these patients. Overall, diversion improved biochemical parameters, pruritus, and growth, with substantial variation in individual response. BSEP-common or FIC1 patients survived longer after diversion without developing cirrhosis, being listed for or undergoing liver transplantation, or dying, compared to BSEP-other patients. Transplantation resolved cholestasis in all groups. However, FIC1 patients commonly developed hepatic steatosis, diarrhea, and/or pancreatic disease after transplant accompanied by biochemical abnormalities and often had continued poor growth. In BSEP patients with impaired growth, this generally improved after transplantation. Conclusion: Diversion can improve clinical and biochemical status in FIC1 and BSEP deficiencies, but outcomes differ depending on genetic etiology. For many patients, particularly BSEP-other, diversion is not a permanent solution and transplantation is required. Although transplantation resolves cholestasis in patients with FIC1 and BSEP deficiencies, the overall outcome remains unsatisfactory in many FIC1 patients; this is mainly due to extrahepatic manifestations. (Hepatology Communications 2018;2:515-528).

Tiotropium and simplified detection of dynamic hyperinflation.

STUDY OBJECTIVE: To detect dynamic hyperinflation (DH) by evaluating reduction in inspiratory capacity (IC) during metronome-paced hyperventilation (MPH) in patients with moderate-to-severe COPD, studied before and after treatment with tiotropium. METHODS: IC and FEV(1) were measured before and immediately after MPH at two times resting the respiratory rate for 20 s in 60 COPD patients (28 men; mean age, 66 +/- 10 years [+/- SD]) before and after 30 days of treatment with tiotropium bromide, 18 mug. Patients were encouraged to maintain a constant tidal volume during MPH. RESULTS: At baseline, mean FEV(1) was 1.5 +/- 0.1 L (+/- SE) [57 +/- 1.6% of predicted], mean FVC was 2.6 +/- 0.1L (77 +/- 1.8% of predicted), and mean FEV(1)/FVC was 56 +/- 1%. After 180 mug of aerosolized albuterol sulfate, mean FEV(1) was 1.7 +/- 0.1 L (63 +/- 1.5% of predicted) [p < 0.001] and mean FEV(1)/FVC was 58 +/- 1%. Compared to baseline, after 30 days and 1.5 h after tiotropium there was an increase in IC of 0.18 +/- 0.04L (p < 0.0001); FEV(1) of 0.13 +/- 0.03 L (5.6 +/- 0.8% of predicted; p = 0.0002); FVC of 0.22 +/- 0.05 L (6.5 +/- 1.3% of predicted; p < 0.001); and decrease in end-expiratory lung volume (EELV)/total lung capacity (TLC) of - 3.1 +/- 0.6% (p = 0.0001); a decrease in end-inspiratory lung volume (EILV)/TLC of - 2.9 +/- 1.3% (p = 0.03); and no change in TLC (- 0.06 +/- 0.05 L). Results following MPH-induced DH at baseline and after 30 days of tiotropium were similar, with decreases in IC (- 0.35 +/- 0.03 L; p < 0.001); FEV(1) (- 0.05 +/- 0.04 L; p = 0.2); and FVC (- 0.22 +/- 0.03 L; p < 0.0001); no change in TLC; and increases in EELV/TLC (11.8 +/- 1.0% of predicted; p < 0.0001) and EILV/TLC (4.0 +/- 1.3% of predicted, p < 0.003). CONCLUSION: In patients with moderate-to-severe COPD, tiotropium did not reduce MPH-induced DH and reduction in IC, compared to baseline. However, because tiotropium induced bronchodilation and increased baseline IC, lower operational lung volumes may blunt the effect of MPH-induced DH. The noninvasive simplicity of MPH-induced DH provides a clinically useful screening surrogate to monitor changes in IC following treatment with tiotropium.

Pediatric pancreatic hemangioma: a case report and literature review.

CONTEXT: The pancreas is an unusual site for a hemangioma in an infant. A child with obstructive jaundice caused by a pancreatic hemangioma is presented and management strategies for this benign tumor are discussed. CASE REPORT: A 5-month-old girl presented with a 2-week history of jaundice, pale stools and dark urine. Liver function tests confirmed obstructive jaundice. An abdominal ultrasound scan and magnetic resonance imaging showed an enhancing mass in the head of the pancreas. At laparotomy, a wedge biopsy of the pancreatic tumor was taken and a tube cholecystostomy inserted. Histological examination of the specimen revealed a pancreatic hemangioma with sclerotic features. The high volume of bile loss from the cholecystostomy proved problematic and biliary diversion with a Roux-en-y hepaticojejunostomy was therefore performed. The tumor subsequently regressed spontaneously and was no longer visible on follow-up imaging two years later. The child has since thrived. CONCLUSIONS: Pancreatic hemangiomas are rare and may cause diagnostic confusion. Pancreatic resection should be avoided since the natural history of these benign tumors is that of spontaneous involution. Various strategies can be used to manage any associated obstructive jaundice.

Immediate extubation of children following liver transplantation is safe and may be beneficial.

BACKGROUND: Immediate tracheal extubation of selected adult patients after orthotopic liver transplant (OLT) is common practice. We hypothesized that selected children may be safely extubated immediately after OLT and avoid potentially deleterious effects of artificial ventilation and sedation. METHODS: After June 2002, we chose immediate extubation unless a specific contraindication was identified. Charts of all children undergoing OLT between June 2002 and February 2005 were reviewed to audit safety and outcome of this approach. Comparative data were obtained for children undergoing first elective OLT at other UK centers. RESULTS: Forty-six cadaveric liver transplants were performed in 40 patients: 26 of 34 (76%) elective transplants and 4 of 12 (33%) urgent transplants were extubated immediately after surgery. Eight of 14 (57%) children weighing less than 10 kg were successfully extubated. One child required reintubation after developing transfusion-related acute lung injury. There were no other events compromising patient or graft. Small recipient size, split/reduced grafts, preexisting respiratory disease, retransplantation, and acute liver failure did not individually preclude successful immediate extubation. After elective OLT, the mean duration of intensive care stay was significantly shorter in the extubated group than in those who were ventilated (2.5 vs. 6.1 days, P<0.01). All children receiving a liver transplant at other UK centers in 2003 were ventilated postoperatively. However, the median duration of intensive care stay (2 days) was the same as in our series. CONCLUSIONS: Immediate extubation of selected children after OLT is safe. It may enhance patient recovery, benefit graft physiology, and reduce intensive care requirement.