Aggressive or Moderate Fluid Resuscitation in Acute Pancreatitis.

BACKGROUND: Early aggressive hydration is widely recommended for the management of acute pancreatitis, but evidence for this practice is limited. METHODS: At 18 centers, we randomly assigned patients who presented with acute pancreatitis to receive goal-directed aggressive or moderate resuscitation with lactated Ringer's solution. Aggressive fluid resuscitation consisted of a bolus of 20 ml per kilogram of body weight, followed by 3 ml per kilogram per hour. Moderate fluid resuscitation consisted of a bolus of 10 ml per kilogram in patients with hypovolemia or no bolus in patients with normovolemia, followed by 1.5 ml per kilogram per hour in all patients in this group. Patients were assessed at 12, 24, 48, and 72 hours, and fluid resuscitation was adjusted according to the patient's clinical status. The primary outcome was the development of moderately severe or severe pancreatitis during the hospitalization. The main safety outcome was fluid overload. The planned sample size was 744, with a first planned interim analysis after the enrollment of 248 patients. RESULTS: A total of 249 patients were included in the interim analysis. The trial was halted owing to between-group differences in the safety outcomes without a significant difference in the incidence of moderately severe or severe pancreatitis (22.1% in the aggressive-resuscitation group and 17.3% in the moderate-resuscitation group; adjusted relative risk, 1.30; 95% confidence interval [CI], 0.78 to 2.18; P = 0.32). Fluid overload developed in 20.5% of the patients who received aggressive resuscitation and in 6.3% of those who received moderate resuscitation (adjusted relative risk, 2.85; 95% CI, 1.36 to 5.94, P = 0.004). The median duration of hospitalization was 6 days (interquartile range, 4 to 8) in the aggressive-resuscitation group and 5 days (interquartile range, 3 to 7) in the moderate-resuscitation group. CONCLUSIONS: In this randomized trial involving patients with acute pancreatitis, early aggressive fluid resuscitation resulted in a higher incidence of fluid overload without improvement in clinical outcomes. (Funded by Instituto de Salud Carlos III and others; WATERFALL ClinicalTrials.gov number, NCT04381169.).

Budesonide in the first line treatment of patients with autoimmune hepatitis.

Budesonide is a glucocorticoid characterized by its local action, with a low systemic bioavailability. Since the original trial comparing budesonide with prednisone in 2010, it is recommended as an effective alternative for the treatment of non-severe acute or chronic autoimmune hepatitis. In this document, we review the general pharmacologic properties of glucocorticoids, the available evidence for the use of budesonide as first line option for autoimmune hepatitis as well as the safety profile of the drug.

Congestive Hepatopathy.

Liver disease resulting from heart failure (HF) has generally been referred as "cardiac hepatopathy". One of its main forms is congestive hepatopathy (CH), which results from passive venous congestion in the setting of chronic right-sided HF. The current spectrum of CH differs from earlier reports with HF, due to ischemic cardiomyopathy and congenital heart disease having surpassed rheumatic valvular disease. The chronic passive congestion leads to sinusoidal hypertension, centrilobular fibrosis, and ultimately, cirrhosis ("cardiac cirrhosis") and hepatocellular carcinoma after several decades of ongoing injury. Contrary to primary liver diseases, in CH, inflammation seems to play no role in the progression of liver fibrosis, bridging fibrosis occurs between central veins to produce a "reversed lobulation" pattern and the performance of non-invasive diagnostic tests of liver fibrosis is poor. Although the clinical picture and prognosis is usually dominated by the underlying heart condition, the improved long-term survival of cardiac patients due to advances in medical and surgical treatments are responsible for the increased number of liver complications in this setting. Eventually, liver disease could become as clinically relevant as cardiac disease and further complicate its management.

Association of Smoking with progression from low-risk to high-risk intraductal papillary mucinous neoplasms and pancreatic cancer.

BACKGROUND: Factors associated with the risk of pancreatic adenocarcinoma (PDAC) may play a role in the development and progression of Intraductal Papillary Mucinous Neoplasms (IPMNs). However, data are limited. AIM: To compare exposome factors in three groups of patients with "high or low-risk" IPMNs, as assessed at diagnosis and during a 24-months follow-up, and with PDAC. METHODS: Patients were matched (same sex, age ±5) 1:1. Exposure variables were compared across groups using Kruskal-Wallis, ANOVA, or Chi-square tests with Bonferroni correction. RESULTS: A total of 151 patients were enrolled in each of the three groups (453 overall). The proportion of current smokers was progressively higher in "low-risk", "high-risk" IPMNs and PDAC patients (8.1 %, 11.2 %, 23.3 %; p = 0.0002). The three groups did not differ in terms of ever or heavy smoking, BMI, history of diabetes, cancer, cholecystectomy or chronic pancreatitis, use of statins or aspirin, and family history of cancer. A history of peptic ulcer was more common in PDAC (7.2 %) than in either "low-risk" (2.0 %) or "high-risk" (2.6%) IPMNs (p = 0.02, not significant after Bonferroni correction). CONCLUSION: Active smoking seems associated with the progression of IPMNs to malignancy, and cessation of active smoking might be advised in patients with IPMN.

Is Routine Prophylaxis Against Pneumocystis jirovecii Needed in Liver Transplantation? A Retrospective Single-Centre Experience and Current Prophylaxis Strategies in Spain.

In liver transplant (LT) recipients, Pneumocystis jirovecii pneumonia (PJP) is most frequently reported before 1992 when immunosuppressive regimens were more intense. It is uncertain whether universal PJP prophylaxis is still applicable in the contemporary LT setting. We aimed to examine the incidence of PJP in LT recipients followed at our institution where routine prophylaxis has never been practiced and to define the prophylaxis strategies currently employed among LT units in Spain. All LT performed from 1990 to October 2019 were retrospectively reviewed and Spanish LT units were queried via email to specify their current prophylaxis strategy. During the study period, 662 LT procedures were carried out on 610 patients. Five cases of PJP were identified, with only one occurring within the first 6 months. The cumulative incidence and incidence rate were 0.82% and 0.99 cases per 1000 person transplant years. All LT units responded, the majority of which provide prophylaxis (80%). Duration of prophylaxis, however, varied significantly. The low incidence of PJP in our unprophylaxed cohort, with most cases occurring beyond the usual recommended period of prophylaxis, questions a one-size-fits-all approach to PJP prophylaxis. A significant heterogeneity in prophylaxis strategies exists among Spanish LT centres.