Utility of Lumbar Puncture in Children Presenting With Status Epilepticus.

OBJECTIVES: Because meningitis may trigger seizures, we sought to determine its frequency in children with first-time status epilepticus (SE). METHODS: We performed a retrospective cross-sectional study of children aged 1 month to 21 years who presented to a single pediatric emergency department between 1995 and 2012 with SE and who had a lumbar puncture (LP) performed as part of the diagnostic evaluation. We defined bacterial meningitis as a cerebrospinal fluid (CSF) culture positive for a bacterial pathogen or CSF pleocytosis (CSF white blood cells ≥10 cells/mm) with a blood culture positive for a bacterial pathogen. We defined viral meningitis or encephalitis using a positive enterovirus or herpes simplex virus polymerase chain reaction test. RESULTS: Among 126 children with SE who had an LP performed, 8 (6%) had CSF pleocytosis. Of these, 5 had received antibiotics before performance of a diagnostic LP. One child in the cohort was proven to have bacterial meningitis (0.8%; 95% confidence interval [CI], 0%-6%). Two other children had enteroviral meningitis (2/13 tested, 15%; 95% CI, 3%-51%), and 1 had a herpes simplex virus infection (1/47, 2%; 95% CI, 0%-15%). CONCLUSIONS: Bacterial meningitis is an uncommon cause of SE.

Impact of EGF, IL28B, and PNPLA3 polymorphisms on the outcome of allograft hepatitis C: a multicenter study.

Hepatitis C virus (HCV) infection is accelerated following liver transplantation (LT). Single nucleotide polymorphisms (SNPs) near the epidermal growth factor (EGF) (rs4444903), IL28B (rs12979860), and PNPLA3 (rs738409) loci are associated with treatment response, fibrosis, and hepatocellular carcinoma in non-transplant hepatitis C, but allograft population data are limited. We sought to determine the role of these SNPs in 264 patients with HCV who underwent LT between 1990 and 2008. Genotypes were determined from donor wedge/allograft biopsies and recipient explants. Cox proportional hazards model was used to assess time to cirrhosis, liver-related death, and retransplantation, adjusting for donor age and sustained virological response (SVR). Over a median follow-up of 6.3 yr, a trend toward increased progression to graft cirrhosis was observed among recipients of an EGF non-AA vs. AA donor liver (adjusted HR 2.01; 95% CI 0.93-4.34; p = 0.08). No other genotypes predicted cirrhosis development or graft survival. The CC IL28B variant in both recipients and donors was associated with increased rate of SVR (R-CC/D-CC 8/12[67%], R-non-CC/D-CC or R-CC/D-non-CC 23/52[44%], R-non-CC/D-non-CC 12/45[27%], p linear trend = 0.009). Recipient EGF, IL28B, and PNPLA3, and donor IL28B and PNPLA3 genotypes do not predict adverse outcomes in HCV LT recipients. A potential association exists between donor EGF genotype and cirrhosis.

Yield of emergent neuroimaging in children with new-onset seizure and status epilepticus.

PURPOSE: To determine the yield of emergent neuroimaging among children with new-onset seizures presenting with status epilepticus. METHOD: We performed a cross-sectional study of children seen at a single ED between 1995 and 2012 with new-onset seizure presenting with status epilepticus. We defined status epilepticus as a single seizure or multiple seizures without regaining consciousness lasting 30 min or longer. Our primary outcome was urgent or emergent intracranial pathology identified on neuroimaging. We categorized neuroimaging results as emergent if they would have changed acute management as assessed by a blinded neuroradiologist and neurologist. To ensure abnormalities were not missed, we review neuroimaging results for 30 days following the initial episode of SE. RESULTS: We included 177 children presenting with new-onset seizure with status epilepticus, of whom 170 (96%) had neuroimaging performed. Abnormal findings were identified on neuroimaging in 64/177 (36%, 95% confidence interval 29-43%) children with 15 (8.5%, 95% confidence interval 5.2-14%) children having urgent or emergent pathology. Four (27%) of the 15 children with urgent or emergent findings had a normal non-contrast computed tomography scan and a subsequently abnormal magnetic resonance image. Longer seizure duration and older age were associated with urgent or emergent intracranial pathology. CONCLUSION: A substantial minority of children with new-onset seizures presenting with status epilepticus have urgent or emergent intracranial pathology identified on neuroimaging. Clinicians should strongly consider emergent neuroimaging in these children. Magnetic resonance imaging is the preferred imaging modality when available and safe.

Reduced Albumin Dosing During Large-Volume Paracentesis Is Not Associated with Adverse Clinical Outcomes.

BACKGROUND: LVP is used to manage diuretic-resistant ascites in cirrhotic patients. Albumin administration prevents complications including acute kidney injury and paracentesis-induced circulatory dysfunction, but the optimal dose is unclear. AIM: We sought to assess adherence to guidelines enacted in July 2011 at our center for reducing the albumin dose administered at large-volume paracentesis (LVP) and evaluate the cost and rate of complications of LVPs before and after guideline enactment. METHODS: All LVPs performed on cirrhotic patients in our center's Department of Radiology between July 2009 and January 2014 were studied. Outcomes included adherence to guidelines, LVP complications, and administered albumin cost. Groups were compared using Student's t tests for continuous data and Chi-square or Fisher's exact tests for categorical data. A repeated measurements model accounted for patients with multiple LVPs. RESULTS: Of the 935 LVPs, 288 occurred before guideline implementation (group 1) and 647 occurred after (group 2). The mean dose of albumin administered was 13.7 g/L of ascites removed in group 1 versus 10.3 g/L in group 2 (p < 0.0001). Of the group 2 LVPs, 235 (36.3 %) adhered to guidelines. There were no significant differences in LVP complications. CONCLUSIONS: Guidelines were followed in one-third of LVPs. Despite this limited adherence, a reduction in albumin administration and associated cost savings was still observed. There was no increase in LVP-related complications after guideline implementation or in the adherent group, suggesting that albumin dose can be safely reduced. Future efforts should be directed at enhancing guideline adherence and potentially further reducing albumin dosing.

A genomic and clinical prognostic index for hepatitis C-related early-stage cirrhosis that predicts clinical deterioration.

OBJECTIVE: The number of patients with HCV-related cirrhosis is increasing, leading to a rising risk of complications and death. Prognostic stratification in patients with early-stage cirrhosis is still challenging. We aimed to develop and validate a clinically useful prognostic index based on genomic and clinical variables to identify patients at high risk of disease progression. DESIGN: We developed a prognostic index, comprised of a 186-gene signature validated in our previous genome-wide profiling study, bilirubin (>1 mg/dL) and platelet count (<100,000/mm(3)), in an Italian HCV cirrhosis cohort (training cohort, n=216, median follow-up 10 years). The gene signature test was implemented using a digital transcript counting (nCounter) assay specifically developed for clinical use and the prognostic index was evaluated using archived specimens from an independent cohort of HCV-related cirrhosis in the USA (validation cohort, n=145, median follow-up 8 years). RESULTS: In the training cohort, the prognostic index was associated with hepatic decompensation (HR=2.71, p=0.003), overall death (HR=6.00, p<0.001), hepatocellular carcinoma (HR=3.31, p=0.001) and progression of Child-Turcotte-Pugh class (HR=6.70, p<0.001). The patients in the validation cohort were stratified into high-risk (16%), intermediate-risk (42%) or low-risk (42%) groups by the prognostic index. The high-risk group had a significantly increased risk of hepatic decompensation (HR=7.36, p<0.001), overall death (HR=3.57, p=0.002), liver-related death (HR=6.49, p<0.001) and all liver-related adverse events (HR=4.98, p<0.001). CONCLUSIONS: A genomic and clinical prognostic index readily available for clinical use was successfully validated, warranting further clinical evaluation for prognostic prediction and clinical trial stratification and enrichment for preventive interventions.

Host genetics predict clinical deterioration in HCV-related cirrhosis.

Single nucleotide polymorphisms (SNPs) in the epidermal growth factor (EGF, rs4444903), patatin-like phospholipase domain-containing protein 3 (PNPLA3, rs738409) genes, and near the interleukin-28B (IL28B, rs12979860) gene are linked to treatment response, fibrosis, and hepatocellular carcinoma (HCC) in chronic hepatitis C. Whether these SNPs independently or in combination predict clinical deterioration in hepatitis C virus (HCV)-related cirrhosis is unknown. We genotyped SNPs in EGF, PNPLA3, and IL28B from liver tissue from 169 patients with biopsy-proven HCV cirrhosis. We estimated risk of clinical deterioration, defined as development of ascites, encephalopathy, variceal hemorrhage, HCC, or liver-related death using Cox proportional hazards modeling. During a median follow-up of 6.6 years, 66 of 169 patients experienced clinical deterioration. EGF non-AA, PNPLA3 non-CC, and IL28B non-CC genotypes were each associated with increased risk of clinical deterioration in age, sex, and race-adjusted analysis. Only EGF non-AA genotype was independently associated with increased risk of clinical deterioration (hazard ratio [HR] 2.87; 95% confidence interval [CI] 1.31-6.25) after additionally adjusting for bilirubin, albumin, and platelets. Compared to subjects who had 0-1 unfavorable genotypes, the HR for clinical deterioration was 1.79 (95%CI 0.96-3.35) for 2 unfavorable genotypes and 4.03 (95%CI 2.13-7.62) for unfavorable genotypes for all three loci (Ptrend<0.0001). In conclusion, among HCV cirrhotics, EGF non-AA genotype is independently associated with increased risk for clinical deterioration. Specific PNPLA3 and IL28B genotypes also appear to be associated with clinical deterioration. These SNPs have potential to identify patients with HCV-related cirrhosis who require more intensive monitoring for decompensation or future therapies preventing disease progression.

Pediatric status epilepticus: how common is cerebrospinal fluid pleocytosis in the absence of infection?

PURPOSE: To determine the rate of cerebrospinal fluid (CSF) pleocytosis among children presenting with status epilepticus (SE) without proven central nervous system infection. METHOD: We performed a retrospective cross-sectional study of all patients aged one month to 21 years of age who were evaluated in a single pediatric emergency department (ED) for SE between 1995 and 2012. We limited our study to those children who had a CSF culture obtained and excluded those children with proven viral or bacterial infection. We defined SE in a patient who had a single seizure or a cluster of seizures without regaining consciousness which lasted 30 min or longer. We defined CSF pleocytosis as a CSF white blood cells (WBC)>10 cells/mm(3) and a peripheral leukocytosis as WBC ≥ 15,000 cells/mm(3). We compared the rate of CSF pleocytosis between children with and without peripheral leukocytosis using the Fisher's exact test. RESULTS: We identified 289 ED visits for SE, of which 178 (62%) met study inclusion criteria. Seven children (4%, 95% confidence interval 1.7-8.2%) had CSF pleocytosis. More children with peripheral leukocytosis had CSF pleocytosis: (8.6% with peripheral leukocytosis vs. 0.9% without leukocytosis, p=0.01). CONCLUSION: CSF pleocytosis is relatively uncommon among children with prolonged seizures, even in the presence of peripheral leukocytosis. Therefore, all children with CSF pleocytosis after status epilepticus need comprehensive evaluation for central nervous system infection.

Poor adherence to AASLD guidelines for chronic hepatitis B Management and treatment in a large academic medical center.

OBJECTIVES: Adherence to the American Association for the Study of Liver Disease (AASLD) guidelines for the management of chronic hepatitis B (CHB) has not been systematically assessed. We sought to comprehensively evaluate adherence to five key areas of these guidelines. We also evaluated physician and patient factors underlying nonadherence, and predictors of nonadherence such as physician type, patient demographic factors, and phase of CHB infection. METHODS: Nine hundred and sixty-two adult patients were retrospectively identified. Each patient chart was reviewed in detail. The primary outcome was adherence to five areas of the AASLD guidelines: (i) timely alanine aminotransferase (ALT)/hepatitis B virus DNA level checks needed to monitor inactive carrier and immune-tolerant phases; (ii) liver biopsy to guide decisions on initiating treatment; (iii) treatment initiation when indicated; (iv) hepatocellular carcinoma (HCC) screening; (v) testing for hepatitis A virus (HAV) immunity, HIV, and hepatitis C virus (HCV) co-infections. RESULTS: Sixty percent did not undergo clinically indicated liver biopsies, largely owing to physician nonadherence. Eighty-nine percent of these missed biopsies were needed to further assess possible e-antigen-negative CHB. A high treatment initiation rate was found for the treatment eligible, but 121 patients had unclear treatment eligibility as they warranted, but did not undergo, liver biopsy. Forty-five percent did not have timely HCC screening, although gastroenterology physicians had the highest odds of adherence, and 29% did not have timely CHB lab assessment; patients seen by gastroenterologists had twice the odds compared with primary care physicians of undergoing timely lab monitoring. Thirty-five, 24, and 54% were not tested for HAV, HCV, and HIV co-infections. CONCLUSIONS: Our findings show remarkably poor adherence to AASLD guidelines, particularly in the areas of liver biopsy, timely HCC and ALT monitoring, and testing for co-infection. These findings call for greater efforts to meet physician knowledge gaps, incorporation of decision support tools, and improved communication among providers.

Advanced disease, diuretic use, and marital status predict hospital admissions in an ambulatory cirrhosis cohort.

BACKGROUND AND AIMS: Hospital admissions in cirrhotic patients are a source of significant health care expenditure. Most studies to date have focused on readmissions in patients with decompensated cirrhosis. We sought to describe predictors of hospital admissions in an ambulatory cirrhosis cohort consisting of both compensated and decompensated patients to identify patients who could benefit from intensified outpatient chronic disease management. METHODS: We performed a retrospective cohort study of 395 cirrhotic patients followed at an academic medical center liver clinic. Inclusion criteria were documented cirrhosis and longitudinal care at our center during 2006-2008. Patients were followed until December 2011, death, or liver transplantation. The primary outcomes were non-elective cirrhosis-related hospital admissions within 1 year and time to admission. The secondary outcome was 2-year cirrhosis-related mortality. The study was approved by the Partners Human Research Committee (protocol 2012P001912). RESULTS: Seventy-eight patients (19.7 %) had at least one cirrhosis-related hospital admission within 1 year. The following were significant predictors in the multivariable model: model for end-stage liver disease score ≥15 [OR 2.22, 95 % CI (1.21-4.07), p = 0.01], diagnosis of hepatocellular carcinoma [3.64 (1.42-9.35), 0.007], diuretic use [2.27 (1.23-4.17), 0.008], at least one cirrhosis-related admission during the baseline year [2.17 (1.21-3.89), 0.01], and being unmarried [1.92 (1.10-3.35), 0.02]. CONCLUSIONS: Advanced disease, diuretic use, and marital status were associated with cirrhosis-related hospital admissions in patients followed at an academic medical center liver clinic. Our findings suggest that patients with inadequately or overzealously treated ascites, as well as those with limited social supports, could benefit from intensified outpatient management.