Larson, Joseph J.

Nonselective beta‐blockers (NSBBs) have played an important role in the prevention of portal hypertensive bleeding in patients with cirrhosis. However, recent studies have suggested that NSBBs may be harmful in some patients with end‐stage liver disease. The purpose of this article is to evaluate the association between use of NSBB and the incidence of acute kidney injury (AKI). We conducted a nested case‐control study in a cohort of liver transplant wait‐list registrants. Each patient with AKI was matched to a control by the Model for End‐Stage Liver Disease–Na score, age, serum creatinine, and follow‐up duration. Out of a total of 2361 wait‐list registrants, 205 patients developed AKI after a median follow‐up duration of 18.2 months. When compared with matched controls, ascites (79.0% versus 51.7%) and non‐Caucasian race (16.6% versus 7.8%) were more common among the cases. The frequency of NSBB use was higher among the cases than controls, albeit insignificantly (45.9% versus 37.1%; P = 0.08). In multivariate analyses, the impact of nonselective beta blockade on the development of AKI was dependent on the presence of ascites: nonselective beta blockade in patients with ascites significantly increased the risk of AKI (hazard ratio [HR], 3.31; 95% confidence interval [CI], 1.57‐6.95), whereas in patients without ascites, NSBB use reduced it (HR, 0.19; 95% CI, 0.06‐0.60). Potential benefits and harms of a NSBB in terms of AKI depend on the presence of ascites in liver transplant candidates. NSBB therapy in patients with cirrhosis may need to be individualized. Liver Transplantation 23 733–740 2017 AASLD.

Acute on chronic liver failure (ACLF) is associated with multisystem organ failure and poor prognosis in hospitalized patients with cirrhosis. We aimed to determine time trends in the epidemiology, economic burden, and mortality of ACLF in the United States. The National Inpatient Sample database was queried between 2001 and 2011. ACLF was defined as two or more extrahepatic organ failures in patients with cirrhosis. The primary outcomes were trends in hospitalizations, hospital costs, and inpatient mortality. The number of hospitalizations for cirrhosis in the United States nearly doubled from 371,000 in 2001 to 659,000 in 2011. The prevalence of ACLF among those hospitalizations increased from 1.5% (n = 5,400) to 5% (n = 32,300). The inpatient costs increased 2‐fold for cirrhosis ($4.8 billion to $9.8 billion) and 5‐fold ($320 million to $1.7 billion) for ACLF. In 2011, the cost per hospitalization for ACLF was 3.5‐fold higher than that for cirrhosis ($53,570 versus $15,193). The in‐hospital fatality rates decreased from 65% to 50% for ACLF and from 10% to 7% for cirrhosis. The organ failure trends in ACLF showed an increasing proportion of cardiovascular and cerebral and decreasing proportion of respiratory and renal failure. Age, male sex, and the number and types of organ failure were predictors of death in ACLF. Conclusion: Cirrhosis and ACLF represent a substantial and increasing health and economic burden in the United States; these data highlight an urgent need for research on pathophysiological mechanisms and effective therapy as well as for education of health care providers of its importance in the care of patients with cirrhosis. (H epatology 2016;64:2165‐2172).

Objective Fukuoka consensus guidelines classify pancreatic cystic lesions (PCLs) presumed to be intraductal papillary mucinous neoplasms (IPMNs) into Fukuoka positive (FP) (subgroups of high-risk (HR) and worrisome features (WFs)) and Fukuoka negative (FN) (non-HR feature/WF cysts). We retrospectively estimated 5-year risk of pancreatic cancer (PC) in FN, WF and HR cysts of patients with PCL-IPMN. Design From Mayo Clinic databases, we randomly selected 2000 patients reported to have a PCL; we excluded inflammatory or suspected non-IPMN cysts and those without imaging follow-up. We re-reviewed cross-sectional imaging and abstracted clinical and follow-up data on PCL-IPMNs. The study contained 802 patients with FN cysts and 358 with FP cysts. Results Patients with PCL-IPMN had median (IQR) follow-up of 4.2 (1.8–7.1) years. Among FN cysts, 5-year PC risk was low (2–3%) regardless of cyst size (p=0.67). After excluding events in the first 6 months, 5-year PC risk remained low (0–2%) regardless of cyst size (p=0.61). Among FP cysts, HR cysts (n=66) had greater 5-year PC risk than WF cysts (n=292) (49.7% vs 4.1%; p<0.001). In HR cysts, 3-year PC risk was greatest for obstructive jaundice versus enhancing solid component or main pancreatic duct >10 mm (79.8% vs 37.3% vs 39.4%, respectively; p=0.01). Conclusions Fukuoka guidelines accurately stratify PCL-IPMNs for PC risk, with FN cysts having lowest and HR cysts having greatest risk. After 6-month follow-up, WF and FN cysts had a low 5-year PC risk. Surveillance strategies should be tailored appropriately.

Summary Background To date there have been no clear features that aid in differentiating patients with eosinophilic oesophagitis (EoE) from PPI ‐responsive oesophageal eosinophilia ( PPI ‐ REE ). However, barium swallow roentgenography is a more sensitive and specific measure to detect subtle fibrostenotic remodeling changes present in EoE. We aim to characterise any clinical, endoscopic, histiological or barium roentgenographic differences between EoE and PPI ‐ REE . Aim To characterise any clinical, endoscopic, histiological or barium roentgenographic differences between EoE and PPI ‐ REE . Methods We performed a retrospective cohort analysis on data collected from a tertiary referral centre population from 2010 to 2015. Data from 66 patients with EoE and 28 patients with PPI ‐ REE were analysed. Cases were adults who met consensus guidelines for EOE , and had a barium swallow study within 6 months of the index endoscopy. Clinical, endoscopic, histiological and barium swallow findings were collected. Results Patients with EoE reported similar characteristics as PPI ‐ REE patients, except EoE patients were younger (35.6 vs. 46.6 years; P = 0.011), had earlier symptom onset (29.0 vs. 38.0 years; P = 0.026), and smaller oesophageal diameters on barium swallow (19.5 mm vs. 20; P = 0.042). Patients with EoE were more likely to have distal strictures (EoE 77% vs. 25%; P = 0.02) and, importantly, a greater likelihood of small calibre oesophagus (51.5% vs. 17.9%; P = 0.002). Moreover, EoE patients had a higher probability of developing small calibre oesophagus after 20 years of symptoms (72.3% vs. 30.2%; P = 0.074) compared to PPI ‐ REE patients. Conclusions When compared with eosinophilic oesophagitis, PPI ‐ REE patients demonstrate findings that suggest PPI‐responsive oesophageal eosinophilia to be a later onset, less aggressive form of oesophageal stricturing disease than eosinophilic oesophagitis.

Non‐invasive tests to identify age and early disease‐associated pathology within the kidney are needed. Specific populations of urinary extracellular vesicles (EVs) could potentially be used for such a diagnostic test. Random urine samples were obtained from age‐ and sex‐stratified living kidney donors before kidney donation. A biopsy of the donor kidney was obtained at the time of transplantation to identify nephron hypertrophy (larger glomerular volume, cortex per glomerulus and mean profile tubular area) and nephrosclerosis (% fibrosis, % glomerulosclerosis and arteriosclerosis). Renal parenchymal‐derived EVs in cell‐free urine were quantified by digital flow cytometry. The relationship between these EV populations and structural pathology on the kidney biopsy was assessed. Clinical characteristics of the kidney donors (n=138, age range: 20–70 years, 50% women) were within the normative range. Overall, urine from women contained more EVs than that from men. The number of exosomes, juxtaglomerular cells and podocyte marker–positive EVs decreased (p<0.05) with increasing age. There were fewer total EVs as well as EVs positive for mesangial cell, parietal cell, descending limb of Henle's loop (simple squamous epithelium), collecting tubule‐intercalated cell and monocyte chemoattractant protein‐1 markers (p<0.05) in persons with nephron hypertrophy. The number of EVs positive for intercellular adhesion molecule‐1, juxtaglomerular cell, podocyte, parietal cell, proximal tubular epithelial cell, distal tubular epithelial cell and collecting duct cells were fewer (p<0.05) in persons with nephrosclerosis. EVs carrying markers of cells from the renal pelvis epithelium did not associate with any indices of nephron hypertrophy or nephrosclerosis. Therefore, specific populations of EVs derived from cells of the glomerulus and nephron associate with underlying kidney structural changes. Further validation of these findings in other cohorts is needed to determine their clinical utility.

AbstractBackgroundThe etiology of irritable bowel syndrome (IBS) is not been fully elucidated, but childhood trauma may disturb the brain–gut axis and therefore be important. Thus, we conducted a family based case–control study of IBS cases and their relatives with the aims to (i) determine the frequency of childhood trauma among IBS cases and controls as well as their relatives, and (ii) assess childhood trauma among IBS cases with affected relatives (familial IBS).MethodsOutpatients with IBS, matched controls, and their first‐degree relatives completed a self‐report version of Bremner' Early Trauma Inventory. Percent of cases and controls with a family history were compared and odds ratios were computed using chi‐squared test; recurrence risks to relatives were computed using logistic regression and generalized estimating equations.Key ResultsData were collected from 409 cases, 415 controls, 825 case relatives, and 921 control relatives. IBS cases had a median age of 50 and 83% were women. Of IBS cases, 74% had experienced any general trauma compared to 59% among controls, yielding an odds ratio of 1.56 (95% CI: 1.13–2.15, p < 0.008). There were no statistical differences between IBS relatives and control relatives with regards to lifetime trauma.Conclusions & InferencesIBS is associated with childhood trauma, and these traumas often occur prior to onset of IBS symptoms. This provides further insight into how traumatic childhood events are associated with development of adult IBS.