Milneshapiro6302

The aim of the study was to examine the frequency of rickets and bone fractures and to assess areal bone mineral density (aBMD) in childhood among patients with biliary atresia (BA).

We gathered data on all patients diagnosed with BA in Finland that survived to ≥1 year of age between 1 January 2000 to 30 June 2018. Data on gestational age, birth weight, postsurgical medications, and history of rickets and bone fractures were collected retrospectively. Serum levels of 25-hydroxyvitamin D [25(OH)D] postportoenterostomy (PE) were collected. Plain radiographs and dual energy X-ray absorptiometry (DXA) measurements of study subjects were reviewed.

Out of 49 patients, 7 (14%) were diagnosed with rickets during infancy. Clearance of jaundice [odds ratio 0.055, 95% confidence interval [CI] 0.00266-0.393; P < 0.01] was a protective factor against rickets. Sufficient 25(OH)D levels were reached 3 months post-PE. Eleven (22%) patients suffered at least one bone fracture (range 1-9) during childhood and adolescence. In DXA measurements, median lumbar spine aBMD anthropometrically adjusted z-scores were as follows in native liver survivors 0.8 (interquartile range [IQR] -1.9 to 1.4) at 5 and -0.3 (IQR -1.3 to 0.8) at 10 years and for liver transplanted patients 0.4 (IQR -0.2 to 1.1) at 5 and 0.6 (IQR -0.1 to 1.3) at 10 years.

BA patients have an increased risk for rickets and bone fractures compared with the normal population. Most BA patients have aBMD within normal range between 5 and 10 years of age irrespective of liver transplantation status.

BA patients have an increased risk for rickets and bone fractures compared with the normal population. Most BA patients have aBMD within normal range between 5 and 10 years of age irrespective of liver transplantation status.

In many pediatric acute liver failure (PALF) cases, a diagnosis is not identified, and the etiology is indeterminate (IND-PALF). Our pilot study found dense CD8 T-cell infiltrates and increased T-cell clonality in liver specimens from IND-PALF patients. We aimed to validate these findings in a multicenter cohort with investigators blinded to diagnosis.

PALF Study Group registry subjects with IND-PALF (n = 37) and known diagnoses (DX-PALF) (n = 18), ages 1 to 17 years, with archived liver tissue were included. Liver tissue slides were stained for T cells (CD8 and CD4), B cells (CD20), macrophages (CD163), perforin, and tissue resident-memory T cells (Trm, CD103), and scored as minimal, moderate, or dense. Lymphocytes were isolated from frozen liver tissue for T-cell receptor beta (TCRβ) sequencing.

Dense hepatic CD8 staining was found in significantly more IND-PALF (n = 29, 78%) compared with DX-PALF subjects (n = 5, 28%) (P = 0.001). IND-PALF subjects were more likely to have dense or moderate perforin are needed to characterize potential antigens, host risk factors, and inflammatory pathways with the goal of developing targeted therapies.

Acute exacerbations of inflammatory bowel disease (IBD) may involve enteric pathogen. We aimed to assess the frequency and outcomes of Clostridium difficille toxin (CDT) and non-CDT enteric infections in symptomatic pediatric patients with IBD.

Patients' records were retrospectively searched for disease flares in which stool samples were collected for enteric pathogens. Each patient with a positive sample was matched with a patient with IBD flare and negative samples for analyzing 1-year outcomes following sampling.

A total of 618 pediatric patients with IBD [Crohn's disease, n = 439 (71%), mean age at diagnosis 13.0 ± 3.4 years, girls, n = 264 (42.7%)] had 1048 stool samples during the study period (2001-2018). Of 914 bacterial cultures, 40 (4.3%) were positive, 30 (75%) of which, positive for Campylobacter jejuni. Of 393 samples for CDT, 28 (7.1%) were positive while parasitic infection rate was 21/529 (3.9%).Overall, 19 positive C jejuni cases and 19 positive CDT cases with matching controls were examined. During 12 months of follow-up, the mean number of disease flares and emergency room visits was higher among patients with positive CDT (1.5 ± 1.4 vs 0.5 ± 0.9, P = 0.019, 1.3 ± 1.5 vs 0.4 ± 0.8, P = 0.05, respectively) with a numeric increase of surgical interventions (3 vs 0, P = 0.08). There were no significant differences in disease outcomes between patients with C jejuni infections and matched controls.

C difficile and C jejuni are the most common enteric infections among pediatric patients with IBD but only clostridial infection was associated with a more severe disease course within 12 months.

C difficile and C jejuni are the most common enteric infections among pediatric patients with IBD but only clostridial infection was associated with a more severe disease course within 12 months.

In this study we investigated the role of the Cannabinoid Receptor type 2 (CB2) in the bone loss associated with Celiac Disease (CD) evaluating the effect of its pharmacological modulation on osteoclast activity. We previously demonstrated a significant association between the CB2 Q63R variant and CD, suggesting it as a possible disease biomarker. Moreover, CB2 stimulation is beneficial for reducing osteoclast activity in several bone pathologic conditions.

in vitro osteoclasts (OCs) were differentiated from peripheral blood mononuclear cells of healthy donors, CD children at diagnosis and after one year of gluten free diet (GFD) and characterized by Real Time PCR and Western Blot for the expression of CB2 and specific osteoclastic markers, TRAP and Cathepsin K. TRAP assay and Bone Resorption assay were performed to evaluate osteoclast activity before and after 48 h exposure to CB2 selective drugs (JWH-133 and AM630) and Vitamin D.

We found in CD patients an osteoclast hyper-activation and low levels of CB2. CB2 stimulation with JWH-133 agonist is more effective than Vitamin D in reducing osteoclast activity while CB2 blockade with AM630 increases osteoclast activation. The anti-osteoporotic effect of JWH-133 decreases when used in co-treatment with vitamin D. GFD reduces osteoclast activity without restore CB2 expression.

CB2 could be a molecular marker to predict the risk of bone alterations in CD and a pharmacological target to reduce bone mass loss in patients who need a direct intervention on bone metabolism, in addition to the GFD.

CB2 could be a molecular marker to predict the risk of bone alterations in CD and a pharmacological target to reduce bone mass loss in patients who need a direct intervention on bone metabolism, in addition to the GFD.

Acute-on-chronic liver failure (ACLF), whereas increasingly well-defined in adults, has been poorly characterized in pediatric patients other than having a poor prognosis. This study aimed to identify ACLF and evaluate prognosis in the American pediatric population.

Modified ACLF definitions (p-CLIF) were applied to 11,300 children listed for liver transplantation from March 2002 through 2017 in the Organ Procurement and Transplantation Network (OPTN) database.

Pediatric ACLF patients have greater mortality within 90 days from listing (46.6% by p-CLIF) than other types of failure (<30%), including acute liver failure, as well as greater mortality within the first 30 and 90 days after transplantation than all other types of liver failure, but do not have increased mortality rates relative to other groups between 90 and 365 days from transplant. Although some ACLF listings also received 1B status, ACLF mortality at 90 days was greater than the general 1B population (50 vs 29.4%). Model for End-Stage Liindicate greater attention to ACLF is needed, as scoring systems may not capture these children's risk of early death, which appears to currently be mitigated by exceptions. Multicenter, clinical, preferably prospective study of ACLF is necessary to determine how to prioritize ACLF relative to other liver failure types to address its relatively higher early mortality.

Autoimmune hepatitis (AIH) is designated as type 1 or 2 (AIH-1/2) on the basis of serum autoantibody (Ab) profiles. In children, AIH may present as acute or chronic liver failure or cirrhotic AIH (ALF/CLF/CAIH) with or without overlap sclerosing cholangitis (SC). The aim of this study was to compare demographics, presentation, and outcomes between groups in children.

A retrospective electronic chart review of children with AIH who met standard diagnostic criteria with histologic confirmation at Texas Children's Hospital was performed, with de novo AIH after liver transplant (LT) excluded. Patients were identified and divided into AIH-1, AIH-2, ALF, CAIH, AIH-SC, and LT and compared using chi-square analysis, Student t-test, and Mood median test.

Among 91 children with AIH, 72 (79.1%) had AIH-1, 19 (20.9%) had AIH-2, 13 (14.3%) had ALF, 25 (27.5%) had CAIH, and 14 (15.4%) had AIH-SC. Both AIH-1/2 had female and Hispanic predominance (72.2/89.5%, 40.3/57.9%). AIH-2 presented at younger mean age in years than AIH-1 (6.8, 12.1, P < 0.05). Both AIH-1/2 had low rates of remission after 1 year of IS (25.4, 35.7%) and most recent (30.6, 54.5%) follow-up. Twenty-two (24.2) patients received LT 16 had AIH-1 (72.7%), 6 had AIH-2 (27.3%), 9 (40.9%) had ALF, and 13 (59.1%) had CAIH. One-year patient and graft survivals were 100%.

The epidemiology and clinical presentation of AIH-1 and -2 had a few subtle differences. AIH-1 was associated with more complications after LT. More data are needed to better characterize the 2 as separate disease entities.

The epidemiology and clinical presentation of AIH-1 and -2 had a few subtle differences. AIH-1 was associated with more complications after LT. More data are needed to better characterize the 2 as separate disease entities.

Prophylactic colectomy at a premalignant stage is the cornerstone of management of familial adenomatous polyposis (FAP). Prior to surgery, colonoscopy surveillance is recommended in children with FAP. This study aimed to examine the natural history of FAP in children by evaluating adenoma progression and factors influencing timing of colectomy.

Patients with FAP under the age of 18 years at first surveillance colonoscopy and who had undergone more than one colonoscopy were identified. Demographic, endoscopic, genetic and surgical data were retrieved. Cumulative adenoma (polyp) counts were obtained whilst accounting for any polypectomies during the study period. The rate of polyp progression and factors influencing the timing of colectomy.were evaluated.

Eighty-four patients (50% male; mean age at first colonoscopy 13 years [SD 1.97]) were identified, of which 83 had a family history of FAP. At first colonoscopy, 67 (79%) had <100 adenomas and 29 (35%) had colonic polyps identified despite rectal sparing. The median rate of polyp progression per patient was 12.5 polyps/year (range 0-145). BI-3812 Of the 45 (54%) patients who had undergone surgery, 41 (91%) underwent colectomy with ileorectal or ileodistal sigmoid anastomosis. Polyp progression did not alter the choice of surgical intervention in any patient.

Our results suggest that adenoma number remains relatively stable in the majority of children under surveillance. Tailored surveillance intervals according to phenotype are a more appropriate strategy as recommended by recently published guidelines.

Our results suggest that adenoma number remains relatively stable in the majority of children under surveillance. Tailored surveillance intervals according to phenotype are a more appropriate strategy as recommended by recently published guidelines.