Serum biomarkers correlated with liver stiffness assessed in a multicenter study of pediatric cholestatic liver disease.

Background And Aims: Detailed investigation of the biological pathways leading to hepatic fibrosis and identification of liver fibrosis biomarkers may facilitate early interventions for pediatric cholestasis.

Approach And Results: A targeted enzyme-linked immunosorbent assay-based panel of nine biomarkers (lysyl oxidase, tissue inhibitor matrix metalloproteinase (MMP) 1, connective tissue growth factor [CTGF], IL-8, endoglin, periostin, Mac-2-binding protein, MMP-3, and MMP-7) was examined in children with biliary atresia (BA; n = 187), alpha-1 antitrypsin deficiency (A1AT; n = 78), and Alagille syndrome (ALGS; n = 65) and correlated with liver stiffness (LSM) and biochemical measures of liver disease. Median age and LSM were 9 years and 9.

A two decade long study of disease progression of de novo and recurrent autoimmune hepatitis in the pediatric population.

Recurrent autoimmune hepatitis (rAIH) occurs in patients who undergo liver transplantation (LT) for AIH and de novo AIH (dAIH) is seen in patients who are transplanted for etiologies other than AIH. Whether these are distinct diseases with a similar phenotype remains understudied. The aim of this study was to identify clinical and immunologic factors affecting outcome in patients with dAIH and rAIH.

Pediatric Right Ventricular Cardiac Steatosis following Immunosuppressive Treatment.

Right ventricular myocardial fatty infiltration has been observed in pediatric cardiac allografts with an associated decrease in graft life expectancy. A possible explanation included an immunosuppressant drug effect which prompted us to examine common factors between non-cardiac transplanted immunosuppressed patients and postmortem hearts of pediatric patients who died of non-cardiac causes. Sixty-one of 1,030 pediatric autopsies were from immunosuppressed children who were treated with corticosteroids for malignant tumors, non-cardiac transplantations, or other chronic clinical conditions.

Necrotizing fasciitis caused by Mucor indicus in a pediatric bone marrow transplant recipient.

Necrotizing fasciitis is a life-threatening, rapidly progressing infection of fascia and subcutaneous cellular tissue typically caused by mixed aerobic and anaerobic bacteria. We present a case report of an immunocompromised 4-year-old female with necrotizing fasciitis from a rare fungal organism, Mucor indicus. The patient underwent multiple debridements and was treated for 10 months, first on liposomal amphotericin B (2 months) then posaconazole (8 months).

Paracrine Effects of Leydig Cell Nodular Hyperplasia, Two Case Reports: A Neglected Phenomenon.

Leydig cell nodular hyperplasia (LCNH) is a lesion that is less characterized than the familiar Leydig cell tumors. The paracrine effects of these lesions on adjacent gonadal stroma have not been widely documented. We present two cases of precocious puberty in pre-pubertal boys found to have a single LCNH with adjacent focal maturation of the seminiferous tubules.

Suppurative Granulomatous Cholecystitis in a Pediatric Chronic Carrier with Salmonella enterica serotype Typhi: A Case Report and Review of Literature.

Bacterial infection of Salmonella enterica serotype Typhi is rare in the United States but endemic in many developing countries. Approximately 3-5% of patients become chronic asymptomatic carriers. We describe an atypical presentation of S.

Giovanni Battista Morgagni (1682-1771), the First Pediatric Pathologist.

During the age of enlightenment in the 18th century, radical changes were occurring in the Western world in science, medicine, philosophy, religion, and socio-economic concepts. In medicine, major advances had already been underway since the days of Vesalius.

Contrast-Based Real-Time Assessment of Microcirculatory Changes in a Fatty Liver After Ischemia Reperfusion Injury.

Objectives: A fatty liver is known to have impairment of microcirculation, which is worsened after ischemia reperfusion injury (IRI). This makes most fatty grafts unsuitable for transplantation, and in the absence of real time assessment of microcirculation this selection has been at best, random. The aim of this study was to demonstrate the utility of a contrast enhanced ultrasound model in quantitative assessment of the microcirculation of a fatty liver.

Identification of Bile Duct Paucity in Alagille Syndrome: Using CK7 and EMA Immunohistochemistry as a Reliable Panel for Accurate Diagnosis.

Bile duct paucity is the absence or marked reduction in the number of interlobular bile ducts (ILBD) within portal tracts. Its syndromic variant, Alagille syndrome (ALGS), is a multisystem disorder with effects on the liver, cardiovascular system, skeleton, face, and eyes. It is inherited as an autosomal dominant trait due to defects in NOTCH signaling pathway.

Thoracoschisis: A Case Report and Review of Literature.

Thoracoschisis is an extremely rare congenital birth defect in which intra-abdominal organs eviscerate through a defect in the thoracic wall(1). There are only seven previously reported pediatric cases and in each case, there is some diaphragmatic anomaly, suggesting that the defect took place before complete formation of the diaphragm. Our patient was referred to us from a local hospital immediately after delivery.

Mitigation of autophagy ameliorates hepatocellular damage following ischemia-reperfusion injury in murine steatotic liver.

Ischemia-reperfusion injury (IRI) is a common clinical consequence of hepatic surgery, cardiogenic shock, and liver transplantation. A steatotic liver is particularly vulnerable to IRI, responding with extensive hepatocellular injury. Autophagy, a lysosomal pathway balancing cell survival and cell death, is engaged in IRI, although its role in IRI of a steatotic liver is unclear.

Concomitant a novel ALAS2 mutation and GATA1 mutation in a newborn: a case report and review of the literature.

GATA-1, an X-linked gene, encodes a transcription factor that plays a role in erythropoiesis and megakaryopoiesis. GATA-1 mutations have been associated with various diseases, such as X-linked thrombocytopenia. ALAS2 is an X-linked erythroid-specific isoenzyme expressed during erythropoiesis.

Malakoplakia and primary immunodeficiency.

Malakoplakia, a rare granulomatous disease caused by impaired macrophage response, has been reported only rarely in children. We report 3 unique cases, with lesions occurring in unusual locations in children with primary immune deficiencies.

Placental findings in singleton stillbirths.

Objective: To compare placental lesions for stillbirth cases and live birth controls in a population-based study.

Methods: Pathologic examinations were performed on placentas from singleton pregnancies using a standard protocol. Data were analyzed overall and within gestational age groups at delivery.

Noniatrogenic neonatal gastric perforation: the role of interstitial cells of Cajal.

Noniatrogenic neonatal gastric perforation is a rare and life-threatening condition whose etiology is often unclear. Interstitial cells of Cajal act as gastrointestinal pacemaker cells and express the proto-oncogene c-Kit. Six new cases were identified at our institution which presented with no mechanical, pharmacologic, or otherwise medical-related intervention prior to rupture.

Pathogenic Yersinia DNA in intestinal specimens of pediatric patients with Crohn's disease.

Studies indicate a close relationship between Yersinia and Crohn's disease in adults. Our study tested 77 colonic specimens from children with Crohn's disease for the presence of Yersinia DNA using a validated polymerase chain reaction (PCR) assay. Control cases included specimens from 45 ulcerative colitis patients and 10 appendicitis patients.

Epstein-Barr virus associated smooth muscle tumors in post transplant pediatric patients two cases of rare locations, and review of the literature.

Epstein-Barr virus (EBV) may present few or no symptoms in immunocompetent individuals; however, in immunocompromised patients as in the case of AIDS and post-transplant patients, the virus occasionally stimulates neoplastic transformations. Epstein-Barr virus may play a role in the development of smooth muscle tumors (SMT). In the case of Epstein-Barr associated smooth muscle tumors (EBV+SMT), the virus is thought to be the leading factor to the tumorigenic pathway.

Correlating pathology with the clinical symptoms of methotrexate-induced leukoencephalopathy in a child with relapsed T-cell acute lymphoblastic leukemia.

Intrathecal and systemic methotrexate (MTX), as well as cranial radiation, are effective modalities to prevent central nervous system relapse in childhood acute lymphoblastic leukemia. Leukoencephalopathy is a well-described adverse effect of MTX therapy and is associated with a wide range of neurological sequelae. Most recent studies of MTX-induced leukoencephalopathy have focused exclusively on imaging findings, particularly magnetic resonance imaging.

Clinico-pathologic findings in children with hepatopulmonary syndrome.

Hepatopulmonary syndrome (HPS) is infrequently reported in children. Clinical-pathological findings in 10 HPS children were compared with non-HPS controls. Six patients had cirrhosis and four had noncirrhotic portal hypertension (NCPH) 40%.

The glucagon-like peptide-1 receptor agonist Exendin 4 has a protective role in ischemic injury of lean and steatotic liver by inhibiting cell death and stimulating lipolysis.

Nonalcoholic fatty liver disease is an increasingly prevalent spectrum of conditions characterized by excess fat deposition within hepatocytes. Affected hepatocytes are known to be highly susceptible to ischemic insults, responding to injury with increased cell death, and commensurate liver dysfunction. Numerous clinical circumstances lead to hepatic ischemia.

Bartonella henselae-mediated disease in solid organ transplant recipients: two pediatric cases and a literature review.

Bartonella henselae, the etiologic agent of cat-scratch disease, causes a well-defined, self-limited syndrome of fever and regional lymphadenopathy in immunocompetent hosts. In immunocompromised hosts, however, B. henselae can cause severe disseminated disease and pathologic vasoproliferation known as bacillary angiomatosis (BA) or bacillary peliosis.