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Background: Langerhans cell histiocytosis (LCH) is a rare malignant disorder of epidermal antigen presenting cells. It is characterized by infiltration of various tissues with dendritic cells (Langerhans cells, LC) that express CD1a or CD207 (langerin), often leading to organ dysfunction. A patient with LCH required liver transplantation (LT) for LCH‐associated biliary‐tract disease. Cholangiopathy developed after LT. The question arose: In this patient, did LC in damaged liver‐allograft biliary epithelium signify acute cellular rejection (ACR) or recurrent LCH? Methods: We evaluated immunohistochemical identification of LC (CD1a, CD207) in the proposita and in 14 ACR patient samples as distinguishing between ACR and recurrent LCH. Results: Among 15 patient samples, 3 (20%) marked with neither antibody. Among the remaining 12 samples (80%), 4 (26.7%)—including that from the proposita—had cells marking for both antigens within bile‐duct epithelium as well as in surrounding portal‐tract connective tissue, 2 (13.3%) had cells marking for both antigens in one region or the other, but not in both, and 6 (40%) had cells marking for only one antigen in one region or the other. Conclusions: Immunostaining for CD1a and CD207/langerin in the setting of ACR without suspicion of LCH identifies LC in damaged bile ducts. This biomarker pairing proved not to be LCH‐specific. Our findings indicate that the presence of these cells alone is insufficient to identify recurrent LCH in the allograft liver. [ABSTRACT FROM AUTHOR]

Exome sequencing (ES) has identified biallelic kinesin family member 12 (KIF12) mutations as underlying neonatal cholestatic liver disease. We collected information on onset and progression of this entity. Among consecutively referred pediatric patients at our centers, diagnostic ES identified 4 patients with novel, biallelic KIF12 variants using the human GRCh38 reference sequence, as KIF12 remains incompletely annotated in the older reference sequence GRCh37. A review of these and of 21 reported patients with KIF12 variants found that presentation with elevated serum transaminase activity in the context of trivial respiratory infection, without clinical features of liver disease, was more common (n = 18) than manifest cholestatic disease progressing rapidly to liver transplantation (LT; n = 7). Onset of liver disease was at age <1 year in 15 patients; LT was more common in this group. Serum gamma‐glutamyl transpeptidase activity (GGT) was elevated in all patients, and total bilirubin was elevated in 15 patients. Liver fibrosis or cirrhosis was present in 14 of 18 patients who were biopsied. The 16 different pathogenic variants and 11 different KIF12 genotypes found were not correlated with age of onset or progression to LT. Identification of biallelic pathogenic KIF12 variants distinguishes KIF12‐related disease from other entities with elevated GGT. [ABSTRACT FROM AUTHOR]

Dr. Ron Jaffe, a renowned pediatric pathologist, was known for his exceptionalism, high standards, and compassion. Born in South Africa, he pursued a distinguished career in pathology, specializing in histiocytosis and solid-organ transplantation. Dr. Jaffe's legacy includes mentoring numerous trainees, contributing to over 250 publications, and playing a pivotal role in advancing the study of histiocytoses. His dedication to teaching and his witty sense of humor left a lasting impact on colleagues and friends in the field of pediatric pathology. [Extracted from the article]

Background & aimsThe final step in bile acid synthesis involves conjugation with glycine and taurine, which promotes a high intraluminal micellar concentration to facilitate lipid absorption. We investigated the clinical, biochemical, molecular, and morphologic features of a genetic defect in bile acid conjugation in 10 pediatric patients with fat-soluble vitamin deficiency, some with growth failure or transient neonatal cholestatic hepatitis.MethodsWe identified the genetic defect that causes this disorder using mass spectrometry analysis of urine, bile, and serum samples and sequence analysis of the genes encoding bile acid-CoA:amino acid N-acyltransferase (BAAT) and bile acid-CoA ligase (SLC27A5).ResultsLevels of urinary bile acids were increased (432 ± 248 μmol/L) and predominantly excreted in unconjugated forms (79.4% ± 3.9%) and as sulfates and glucuronides. Glycine or taurine conjugates were absent in the urine, bile, and serum. Unconjugated bile acids accounted for 95.7% ± 5.8% of the bile acids in duodenal bile, with cholic acid accounting for 82.4% ± 5.5% of the total. Duodenal bile acid concentrations were 12.1 ± 5.9 mmol/L, which is too low for efficient lipid absorption. The biochemical profile was consistent with defective bile acid amidation. Molecular analysis of BAAT confirmed 4 different homozygous mutations in 8 patients tested.ConclusionsBased on a study of 10 pediatric patients, genetic defects that disrupt bile acid amidation cause fat-soluble vitamin deficiency and growth failure, indicating the importance of bile acid conjugation in lipid absorption. Some patients developed liver disease with features of a cholangiopathy. These findings indicate that patients with idiopathic neonatal cholestasis or later onset of unexplained fat-soluble vitamin deficiency should be screened for defects in bile acid conjugation.

The Prescription Opioid Misuse Index (POMI) was developed and used in a larger study designed to assess correlates of OxyContin abuse in pain patients prescribed OxyContin, patients treated for OxyContin addiction, and individuals incarcerated for OxyContin-related charges. The POMI was administered to 40 subjects with addiction problems and 34 pain patients who had received OxyContin for pain. Receiver operating characteristic curve analysis indicated that endorsing two or more of six items reliably classified a person as at risk for misuse of their medication. When comparing drug abuse/dependence in subjects classified as misusers or users, significantly more misusers received a diagnosis for alcohol (p < .01), illicit drugs (p < .05), and other prescription medications (p < .05) and reported greater lifetime use of alcohol (p < .002) and illicit drugs (p < .01). No between-group differences were found regarding psychiatric problems. The POMI appears to be a sensitive and specific instrument for identifying patients who misuse opioid medications. Keywords: Screening instrument; Prescription drug abuse; Opioids; Pain

This study investigated the optimal time for measuring stress and immune function in 20 healthcare professionals (19 women and 1 man) following interaction with a therapy dog. A nonclinical sample of healthcare professionals was assigned to 20 min. of quiet rest, and 5 and 20 min. with a therapy dog. Serum cortisol, epinephrine, and norepinephrine were collected at baseline, 5, 15, 30, 45, and 60 min. postcondition. Salivary cortisol, salivary IgA, and blood for lympbocytes were collected at baseline, 30, 45, and 60 min. postcondition. Analysis indicated significant reductions in serum and salivary cortisol. The optimal time for measuring serum or salivary cortisol following interaction with a therapy dog was 45 min., with changes in salivary cortisol reflecting serum cortisol changes. Findings also suggest stress reduction in healthcare professionals may occur after as little as 5 min. of interaction with a therapy dog and warrants further investigation.