Harmsen, William S.

Growing evidence suggests that pretransplant alpha‐fetoprotein (AFP) predicts outcomes of hepatocellular carcinoma (HCC) patients treated with liver transplantation. We aimed to determine whether pretransplant AFP, Lens culinaris agglutinin‐reactive alpha‐fetoprotein (AFP‐L3), and des‐gamma‐carboxyprothrombin (DCP) predicted HCC recurrence after transplantation. A retrospective cohort study of 313 HCC patients undergoing transplantation between 2000 and 2008 was conducted, and 48 (15.3%) developed recurrence during a median follow‐up of 90.8 months. The 127 patients with available serum drawn before transplantation were included; they included 86 without recurrence and 41 with recurrence. Serum was tested for AFP, AFP‐L3%, and DCP in a blinded fashion with the μTASWako i30 immunoanalyzer. All biomarkers were significantly associated with HCC recurrence. The hazard ratios (HRs) were 3.5 [95% confidence interval (CI), 1.9‐6.7; P < 0.0001] for DCP ≥ 7.5 ng/mL and 2.8 (95% CI, 1.4‐5.4; P = 0.002) for AFP ≥ 250 ng/mL. The HR increased to 5.2 (95% CI, 2.3‐12.0; P < 0.0001) when AFP ≥ 250 ng/mL and DCP ≥7.5 ng/mL were considered together. When they were combined with the Milan criteria, the HR increased from 2.6 (95% CI, 1.4‐4.7; P = 0.003) for outside the Milan criteria to 8.6 (95% CI, 3.0‐24.6; P < 0.0001) for outside the Milan criteria and AFP ≥ 250 ng/mL and to 7.2 (95% CI, 2.8‐18.1; P < 0.0001) for outside the Milan criteria and DCP ≥7.5 ng/mL. Our findings suggest that biomarkers are useful for predicting the risk of HCC recurrence after transplantation. Using both biomarkers and the Milan criteria may be better than using the Milan criteria alone in optimizing the decision of liver transplantation eligibility. Liver Transpl 21:599–606, 2015. © 2015 AASLD.

SummaryBackgroundClostridium difficile infection (CDI) recurs in 20–30% of patients.AimTo describe the predictors of recurrence in out‐patients with CDI.MethodsOut‐patient cases of CDI in Olmsted County, MN residents diagnosed between 28 June 2007 and 25 June 2010 were identified. Recurrent CDI was defined as recurrence of diarrhoea with a positive C. difficile PCR test from 15 to 56 days after the initial diagnosis with interim resolution of symptoms. Patients who had two positive tests within 14 days were excluded. Cox proportional hazard models were used to assess the association of clinical variables with time to recurrence of CDI.ResultsThe cohort included 520 out‐patients; 104 had recurrent CDI (cumulative incidence of 17.5% by 30 days). Univariate analysis identified increasing age and antibiotic use to be associated with recurrent CDI. Severe CDI, peripheral leucocyte count and change in serum creatinine >1.5‐fold were not. In a multiple variable model, concomitant antibiotic use was associated with risk of recurrent CDI (HR = 5.4, 95% CI 1.6–17.5, P = 0.005), while age (HR per 10 year increase = 1.1, 95% CI 0.9–1.3, P = 0.22); peripheral leucocyte count >15 × 109/L (HR = 1.0, 95% CI 0.5–2.1, P = 0.92); and change in serum creatinine greater than 1.5‐fold (HR = 0.8, 95% CI 0.4–1.5, P = 0.44) were not.ConclusionsAntibiotic use was independently associated with a dramatic risk of recurrent Clostridium difficile infection in an out‐patient cohort. It is important to avoid unnecessary systemic antibiotics in patients with Clostridium difficile infection, and patients with ongoing antibiotic use should be monitored closely for recurrent infection.

AbstractBackgroundLow basal lower esophageal sphincter (LES) pressure and transient LES relaxations are major causes of gastroesophageal reflux disease (GERD). Pumosetrag, a novel selective partial 5HT3 receptor agonist, showed a promising effect on reducing reflux events in health. We aimed to evaluate the effect of pumosetrag on changes in reflux episodes, lower esophageal sphincter pressure (LESP), and specific symptoms in patients with GERD receiving a refluxogenic meal.MethodsPatients with GERD, who developed heartburn and/or regurgitation after ingestion of a refluxogenic meal, were randomized to 1 of 3 dose levels of pumosetrag (0.2, 0.5, or 0.8 mg) or placebo. Before and after 7 days of treatment, patients underwent manometry, intraesophageal multichannel, intraluminal impedance and pH after a standard refluxogenic meal.Key ResultsA total of 223 patients with GERD [125 (56%) women, mean (SD) age = 36 (12) years] were enrolled. No overall treatment effects were detected for the total number of reflux episodes (acidic and weakly acidic) (p > 0.5); however, significant treatment effects (p < 0.05) on the number of acid reflux episodes were observed with lower values on pumosetrag 0.2 mg (10.8 ± 1.1), 0.5 mg (9.5 ± 1.1), and 0.8 mg (9.9 ± 1.1) compared with placebo (13.3 ± 1.1). Significant treatment effects (p < 0.05) were also observed for the percentage of time pH was <4, with less time for pumosetrag at 0.5 mg (10%) and 0.8 mg (10%) compared with placebo (16%).Conclusions & InferencesIn GERD, the partial 5HT3 agonist pumosetrag significantly reduced the rate of acid reflux events but did not result in a significant change in LESP or symptomatic improvement over a 1‐week treatment period.