Sakil Kulkarni

Use of Pediatric Health Information System database to study the trends in the incidence, management, etiology, and outcomes due to pediatric acute liver failure in the United States from 2008 to 2013

Data were collected of children admitted with ALF to 16 US pediatric liver transplant centers from 2008 to 2013 using the PHIS for a retrospective analysis of PALF trends. Patient data linked to the principal diagnosis code for acute necrosis of the liver (570.00) were analyzed for the following: demographics, regional differences, changes over time, pharmaceutical trends, procedural trends, associated diagnoses, and patient outcomes. In 52.5% of 583 patients who met the selection criteria for PALF, the etiology remained undetermined. Acetaminophen toxicity (18.7%) was the most common identifiable etiology, and hepatic encephalopathy (38.6%) was the most common complication. Mortality was lower than previously reported; 95.4% survived and 73.2% survived without a liver transplant. Acute respiratory failure (OR = 3.4, p = 0.035), acute kidney injury (OR = 3.6, p = 0.003), and cerebral edema (OR = 3.6, p = 0.02) were independently associated with increased risk of mortality. The use of N‐acetylcysteine in non‐acetaminophen‐related ALF, the use of intracranial pressure monitoring, and the proportion of sepsis decreased significantly during the study period. The PHIS database can be a useful tool to study the future trends of PALF patients.

Breast milk is better than formula milk in preventing parenteral nutrition-associated liver disease in infants receiving prolonged parenteral nutrition.

Background and Aim: Breast milk has been shown to be associated with greater success with regard to weaning children with intestinal failure off parenteral nutrition (PN). There are only a few studies investigating the role of breast milk in decreasing PN-associated liver disease (PNALD). The aim of our study was to determine whether breast milk is better than formula milk in preventing PNALD in infants receiving PN for >4 weeks. Methods: We conducted a retrospective analysis of newborns requiring prolonged parenteral nutrition. We divided the sample into 3 different groups (exclusive breast-feeding, exclusive formula-feeding, and mixed feeding. We compared baseline characteristics, feeding profiles and liver function tests, and liver enzymes among the 3 groups. Results: Among infants receiving PN for >4 weeks, we found that infants who were fed only breast milk were significantly less likely to develop PNALD (34.6%) compared with those who were fed only formula milk (72.7%; P = 0.008). The mean maximum conjugated bilirubin (P = 0.03) and the mean maximum aspartate aminotransferase were significantly lower in the breast-fed group (P = 0.04) compared with the formula-fed group. Among the mixed-feeding group, infants who received a higher percentage of breast milk showed a significant negative correlation with the mean maximum conjugated bilirubin. (Pearson correlation −0.517, P = 0.027). The mean number of days receiving PN and the average daily lipid intake in the 2 groups was not significantly different. Conclusions: As a modality for early enteral nutrition, breast milk is protective against the development of PNALD in infants receiving PN for >4 weeks.

Acute Pancreatitis in Pediatric Patients: Demographics, Etiology, and Diagnostic Imaging

OBJECTIVE The objective of this article is to provide updates on acute pancreatitis in children regarding the imaging findings, causes, and complications based on a review of the current studies in the pediatrics literature. We discuss the epidemiology of acute pancreatitis, the role of imaging and imaging findings in the diagnosis of acute pancreatitis, and the causes and complications of acute pancreatitis. CONCLUSION The incidence of acute pancreatitis is increasing in children. Imaging plays an important role in the diagnosis of acute pancreatitis because imaging findings can be used to establish the cause of acute pancreatitis, evaluate for complications of acute pancreatitis, and possibly predict the course of the disease.

Postponing the Hypoglycemic Response to Partial Hepatectomy Delays Mouse Liver Regeneration

All serious liver injuries alter metabolism and initiate hepatic regeneration. Recent studies using partial hepatectomy (PH) and other experimental models of liver regeneration implicate the metabolic response to hepatic insufficiency as an important source of signals that promote regeneration. Based on these considerations, the analyses reported here were undertaken to assess the impact of interrupting the hypoglycemic response to PH on liver regeneration in mice. A regimen of parenteral dextrose infusion that delays PH-induced hypoglycemia for 14 hours after surgery was identified, and the hepatic regenerative response to PH was compared between dextrose-treated and control mice. The results showed that regenerative recovery of the liver was postponed in dextrose-infused mice (versus vehicle control) by an interval of time comparable to the delay in onset of PH-induced hypoglycemia. The regulation of specific liver regeneration-promoting signals, including hepatic induction of cyclin D1 and S-phase kinase-associated protein 2 expression and suppression of peroxisome proliferator-activated receptor γ and p27 expression, was also disrupted by dextrose infusion. These data support the hypothesis that alterations in metabolism that occur in response to hepatic insufficiency promote liver regeneration, and they define specific pro- and antiregenerative molecular targets whose regenerative regulation is postponed when PH-induced hypoglycemia is delayed.

Clinical-radiologic features and treatment of hepatic lesions caused by inadvertent infusion of parenteral nutrition in liver parenchyma due to malposition of umbilical vein catheters

BackgroundUmbilical venous catheterization is a common procedure performed in neonatal intensive care units. Hepatic collections due to inadvertent extravasation of parenteral nutrition into the liver have been described previously in literature.ObjectiveTo recognize the clinicoradiologic features and treatment options of hepatic collections due to inadvertent extravasation of parenteral nutrition fluids caused by malpositioning of umbilical venous catheter (UVC) in the portal venous system.Materials and methodsThis is a case series describing five neonates during a 6-year period at a single tertiary care referral center, with extravasation of parenteral nutrition into the liver parenchyma causing hepatic collections.ResultsAll five neonates receiving parenteral nutrition presented with abdominal distension in the second week of life. Two out of five (40%) had anemia requiring blood transfusion and 3/5 (60%) had hemodynamic instability at presentation. Ultrasound of the liver confirmed the diagnosis in all the cases. Three of the five (60%) cases underwent US-guided aspiration of the collections, one case underwent conservative management and one case required emergent laparotomy due to abdominal compartment syndrome. US used in follow-up of these cases revealed decrease in size of the lesions and/or development of calcifications.ConclusionEarly recognition of this complication, prompt diagnosis with US of liver and timely treatment can lead to better outcome in newborns with hepatic collections secondary to inadvertent parenteral nutrition infusion via malposition of UVC.

MRI-based score helps in assessing the severity and in follow-up of pediatric patients with perianal Crohn disease.

Objectives: The radiologic healing of perianal fistulizing Crohn disease (PfCD) lags behind the clinical healing. Contrast-enhanced pelvic magnetic resonance imaging (MRI) is the radiologic study of choice used to diagnose PfCD in children. The aim was to study whether the various MRI-based radiologic parameters and score can help in staging and follow-up of patients with PfCD. Methods: We performed a retrospective chart review of children with PfCD who underwent contrast-enhanced MRI of the pelvis. The demographic profile, clinical status, and laboratory data of the patients at the time of each MRI examination were noted. Based on the clinical status of the patient at the time of MRI examinations, the MRIs were classified into 3 groups: severe disease, mild-to-moderate disease, and asymptomatic. Each MRI examination was reviewed by a radiologist, who was blinded to the clinical status of the patient. Results: Of the radiologic parameters, the number of fistulas, the complexity of fistulas, and the number of abscesses were significantly lower in the asymptomatic group compared with the mild-to-moderate and severe disease groups. The Van Assche MRI-based score was significantly lower in the asymptomatic group compared with the mild-to-moderate disease (P = 0.01) and the severe disease group (P = 0.002). The percentage increase in fistula activity after gadolinium administration was significantly lower in the asymptomatic group compared with the mild-to-moderate disease (P = 0.026) and severe disease (P = 0.019) groups. The MRI-based scores were significantly higher in the MRI examinations performed at diagnosis compared with those that were performed while the patients were receiving the treatment (P = 0.017). Conclusions: The Van Assche MRI score and the percentage increase in fistula activity after gadolinium administration help in assessing the severity perianal Crohn disease. The Van Assche MRI score may be helpful in documenting healing during therapy of perianal Crohn disease.

An Unusual Case of Pleuropulmonary Blastoma in a Child with Jejunal Hamartomas

We report a rare case of 9-month-old girl who presented with a choking episode and was found to have an incidental finding of a lung cyst and iron deficiency anemia leading to the diagnosis of pleuropulmonary blastoma (PPB) and a jejunal hamartoma. Our patient is the eighth that has been reported with the association of PPB with jejunal hamartoma and the first one in the radiological literature. PPB is the pulmonary analog of other dysontogenetic neoplasms in childhood. A biological sequence has been described with the three types of PPB to be interrelated as part of pathologic progression. PPB can be associated with other cysts and/or neoplasms in different organs. PPB is part of a hereditary neoplasia predisposition syndrome in up to 40% of cases. Mutations in DICER gene have been described with PPB. Hence, a pediatric patient diagnosed with PPB should be screened for associated conditions during childhood and adolescence including intestinal polyps. Obtaining family history for other neoplasms or cysts is important information that should raise the possibility of PPB in pediatric patients with cystic lung lesions. The presence of this syndrome should alert the clinician to screen and follow up patients and their relatives.

Folate Metabolism and Genetic Variant in Down Syndrome: A Meta-Analysis

Objectives: Studies investigating the association between gene polymorphisms involved in homocysteine/folate metabolism and Down syndrome (DS) have reported contradictory or inconclusive results. A meta- analysis of 25 studies on association between MTHFR and MTRR polymorphism and DS including 1, 934/2,081/ cases/controls for MTHFR C677T polymorphism, 1,404/1,632/ cases/control for MTHFR A1298C polymorphism and 859 /1,132/cases/ control for MTRR A66G polymorphism was carried out. Study design: Studies were identified by searching the PubMed database for relevant articles published. Case – control studies were chosen, and odds ratio (OR) with confidence interval (CI) were used to assess the strength of association. Results: The overall results suggested that the variant genotypes MTHFR C677T were associated with DS risk (homozygote, TT vs. CC: OR=2.991; 95% CI: 1.321-3.558; P=0.001 and co dominant model, CT vs. CC: OR=1.1616 (1.216-1.845; P=0.0001). The result of the variant genotypes MTHFR A1298C showed its association with the DS risk (homozygote, AA vs. CC: OR=1.428; 95% CI: 1.016-1.849; P=0.0067).In the stratified analysis, results obtained in variant genotype of MTHFR C677T A66G had increased risk of DS in Caucasian subjects in codominant and dominant model while the increased risk was found in dominant models for Brazilian and Asian subjects. Again, for MTHFR A1298C variant, increased risk was found in Caucasian subject in co-dominant, dominant and recessive models and in co-dominant model for Brazilian population. The results also show that in A66G variant of MTRR had increased risk of DS in both Caucasian and Brazilian subjects in dominant model. Conclusion: This meta-analysis supports the idea that MTHFR C677T and MTHFR A1298C genotype is associated with increased risk for DS.