Comparison of miRNA quantitation by Nanostring in serum and plasma samples.

Circulating microRNAs that are associated with specific diseases have garnered much attention for use in diagnostic assays. However, detection of disease-associated miRNA can be affected by several factors such as release of contaminating cellular miRNA during sample collection, variations due to amplification of transcript for detection, or controls used for normalization for accurate quantitation. We analyzed circulating miRNA in serum and plasma samples obtained concurrently from 28 patients, using a Nanostring quantitative assay platform. Total RNA concentration ranged from 32-125 µg/ml from serum and 30-220 µg/ml from plasma. Of 798 miRNAs, 371 miRNAs were not detected in either serum or plasma samples. 427 were detected in either serum or plasma but not both, whereas 151 miRNA were detected in both serum and plasma samples. The diversity of miRNA detected was greater in plasma than in serum samples. In serum samples, the number of detected miRNA ranged from 3 to 82 with a median of 17, whereas in plasma samples, the number of miRNA detected ranged from 25 to 221 with a median of 91. Several miRNA such as miR451a, miR 16-5p, miR-223-3p, and mir25-3p were highly abundant and differentially expressed between serum and plasma. The detection of endogenous and exogenous control miRNAs varied in serum and plasma, with higher levels observed in plasma. Gene expression stability identified candidate invariant microRNA that were highly stable across all samples, and could be used for normalization. In conclusion, there are significant differences in both the number of miRNA detected and the amount of miRNA detected between serum and plasma. Normalization using miRNA with constant expression is essential to minimize the impact of technical variations. Given the challenges involved, ideal candidates for blood based biomarkers would be those that are indifferent to type of body fluid, are detectable and can be reliably quantitated.

Predictors and impacts of hospital readmissions following liver transplantation.

While liver transplantation is the definitive therapy for end stage liver disease, it remains a major procedure, with many potential complications. Hospital readmissions after the initial hospitalization for liver transplantation can be associated with adverse outcomes, increased cost, and resource utilization. Our aim was to define the incidence and reasons for hospital readmission after liver transplant and the impact of readmissions on patient outcomes. We retrospectively analyzed 30- and 90-day readmission rates and indications in patients who underwent liver transplant at a large-volume transplant center over a 3-year period. Four hundred seventy-nine adult patients underwent their first liver transplant during the study period. The 30-day readmission rate was 29.6%. Recipient and donor age, etiology of liver disease, biological Model for End-Stage Liver Disease score, and cold ischemia time were similar between patients who were readmitted within 30 days and those who were not readmitted. Readmissions occurred in 25% of patients who were hospitalized prior to liver transplant compared to 30% who were admitted for liver transplant. The most common indications for readmission were infection, severe abdominal pain, and biliary complications. Early discharge from hospital (fewer than 7 days after liver transplant), was not associated with readmission; however, a prolonged hospital stay after liver transplant was associated with an increased risk of readmission (p = 0.04). In conclusion, patients who undergo liver transplant have a high rate of readmission. In our cohort, readmissions were unrelated to pre-existing recipient or donor factors, but were associated with a longer hospital stay after liver transplant.

Comparison of endoscopic treatment modalities for Barrett's neoplasia.

BACKGROUND: There are few data comparing endoscopic treatment outcomes for Barrett's esophagus (BE). OBJECTIVE: To compare treatment outcomes in BE patients treated with radiofrequency ablation (RFA), RFA after EMR, and porfimer sodium photodynamic therapy (Ps-PDT). DESIGN: Retrospective, observational study. SETTING: Single tertiary center between 2001 and 2013. PATIENTS: A total of 342 BE patients treated with RFA (n = 119), EMR+RFA (n = 98), and Ps-PDT (n = 125). MAIN OUTCOME MEASUREMENTS: Rates of complete remission of intestinal metaplasia (CRIM), BE recurrence, and adverse events. RESULTS: Baseline BE high-grade dysplasia (HGD) and adenocarcinoma were more common in the Ps-PDT group (89%) compared with the EMR-RFA (70%) and RFA (37%) groups. At a median follow-up of 14.2 months, 173 patients (50.6%) achieved CRIM. CRIM was significantly more common in Ps-PDT patients compared with RFA (P < .001) and EMR-RFA (P < .001) patients on multivariable analysis. In patients who achieved CRIM, the rates of subsequent BE recurrence were relatively similar among the 3 groups. Although the rates of bleeding were similar, strictures were less common in RFA patients (2.4%) compared with EMR-RFA (13.3%, P = .001) and Ps-PDT (10.4%, P =.043) patients. CONCLUSION: This study of endoscopic treatment for Barrett's dysplasia and neoplasia found that complete remission was achieved more often and more rapidly after Ps-PDT with similar disease recurrence rates compared with EMR or RFA. Adverse events were more common after EMR and Ps-PDT. Further studies are required to determine which ablation and resection techniques are ideally suited for each BE patient.

Safety of esophageal EMR in elderly patients.

BACKGROUND: EMR is commonly used to remove suspicious esophageal lesions among patients with Barrett's esophagus (BE). BE primarily affects older patients. Yet, the safety profile of EMR in elderly patients has not been well-described. OBJECTIVE: We aimed to study the safety profile of EMR in elderly patients compared with younger patients. DESIGN: Retrospective, observational, descriptive study that used a prospective database. SETTING: Tertiary-care referral center. PATIENTS: A total of 136 patients who underwent esophageal EMR for BE. INTERVENTIONS: EMR with/without ablative therapy. MAIN OUTCOME MEASUREMENTS: The rate of adverse events, including bleeding, stricture formation, and perforation between elderly (aged ≥75 years) and younger (aged <75 years) patients. RESULTS: We identified 136 patients who underwent esophageal EMR who were followed-up in our clinic. Of those, 40% (n = 55) were aged ≥75 years (elderly group) and 60% (n = 81) were aged <75 years (younger group). There was no difference in rate of stricture formation or early or delayed bleeding when we compared elderly patients to younger patients. None of the patients had esophageal perforation. On multivariable logistic regression analysis, controlling for patient sex, EMR technique, and underlying pathology, older age was not associated with increased odds of adverse events (OR 0.88; 95% confidence interval, 0.42-1.9; P = .75). LIMITATIONS: Single-center experience. CONCLUSION: Rates of adverse events from EMR appear to be similar in elderly patients compared with younger patients. Overall, esophageal EMR seems to offer an acceptable safety profile in elderly patients.

Does erythropoietin cause hemoglobin variability--is it 'normal'?

Hemoglobin variability (Hb-var) in patients with chronic kidney disease has been stipulated to be a result of exogenous treatment with erythropoiesis stimulating agents (ESA) and has been related to mortality in dialysis patients. We hypothesized the existence of Hb-var independent of ESA administration and compared it to that in healthy adults using data from the Scripps-Kaiser and NHANES III databases. We studied the Hb-var in 1571 peritoneal dialysis patients which included 116 patients not requiring treatment with erythropoietin. We systematically studied the differences between the groups that needed ESA therapy and those who did not. White race and male sex were significant predictors of need for erythropoietin therapy. We found peritoneal dialysis patients to exhibit significantly increased Hb-var independent of treatment with exogenous erythropoietin (0.99 gm/dL vs. 1.17 gm/dL, p-value<0.001). We found age to be a significant determinant of Hb-var in the ESA treated group. Hb-var in younger patients (<30 years) was increased by 50% compared to young healthy adults. The Hb-var in elderly (>60 years) peritoneal dialysis patients was similar to that seen in healthy elders, suggesting similarity with anemia of aging. We conclude that exogenous ESA administration does not explain Hb-var entirely but may enhance it. Intrinsic factors affecting erythropoiesis including age may be the major determinants of Hb-var.

Gender differences in remission of esophageal intestinal metaplasia after radiofrequency ablation.

OBJECTIVES: Few studies have assessed the effect of gender on remission rates after radiofrequency ablation (RFA) of Barrett's esophagus (BE). We aim to assess the effect of gender on the time to achieve complete remission of intestinal metaplasia (CRIM) among patients with BE, who underwent RFA. METHODS: This was a retrospective, observational study using a large RFA database in a tertiary referral center. The primary outcome was time to CRIM compared between males and females. Covariates included age, race, smoking history, use of endoscopic mucosal resection (EMR), histology before RFA, and the number of RFA sessions. Time to CRIM (in months) was calculated using the Kaplan-Meier method and compared using the log-rank test. Multivariable Cox-proportional hazard models were used to assess for any association between time to CRIM and gender. RESULTS: Two hundred and fifty-seven patients, 11% (n=23) female, underwent RFA for BE between May 2005 and June 2012. Males and females were similar in mean age, race, smoking history, median BE length, history of EMR, and baseline histology. Median time to CRIM for females was longer than males (24 months (95% confidence interval (CI): 10.3-60.2) vs. 11.7 months (95% CI: 10-15), P=0.03). Using Cox-regression analysis, controlling for age, use of EMR, BE segment length, and the number of RFA sessions, female gender was associated with a 55% decrease in the rate of CRIM compared with that in males (hazard ratio=0.45 (95% CI: 0.25-0.82), P=0.009). CONCLUSIONS: Females take longer time to achieve CRIM when treated with RFA when compared with males of similar age and BE length.

Photodynamic Therapy for Barrett's Esophagus and Esophageal Carcinoma.

This paper reviews the use of photodynamic therapy (PDT) in patients with Barrett's esophagus and esophageal carcinoma. We describe the history of PDT, mechanics, photosensitizers for PDT in patients with esophageal disease. Finally, we discuss its utility and limitations in this setting.