Kia Saeian

Eosinophilic esophagitis in adults: an emerging problem with unique esophageal features

BACKGROUND Eosinophilic esophagitis is an inflammatory condition in which there is dense eosinophilic infiltration of the surface lining of the esophagus. Reports of eosinophilic esophagitis pertain almost exclusively to pediatric populations. However, eosinophilic esophagitis is emerging as a clinical affliction of adults. This report describes the clinical and endoscopic findings of eosinophilic esophagitis in the largest cohort of adult patients reported to date. METHODS Twenty-nine patients (21 men, 8 women; mean age 35 years) with documented eosinophilic esophagitis (>/=15 eosinophils per high-power field in biopsy specimens) and a significant history of chronic dysphagia for solid food (24 patients) were evaluated clinically and endoscopically during a 3-year period (1999-2002). Fourteen patients (48%) had a history of asthma, environmental allergy, or atopy. In a subset of 15 patients, the diagnostic accuracy of endoscopy was compared with that of barium contrast esophagography. RESULTS Twenty-seven patients (93%) had abnormal endoscopic findings; 25 (86%) had unique esophageal structural changes, associated with a preserved mucosal surface, that were highly atypical for acid reflux injury. Structural alterations seen in adult patients with eosinophilic esophagitis may occur in combination or as a primary characteristic, e.g., uniform small-caliber esophagus, single or multiple corrugations (rings), proximal esophageal stenosis, or 1 to 2 mm whitish vesicles scattered over the mucosal surface. Barium contrast radiography combined with swallow of a barium-coated marshmallow identified 10 (67%) of the primary features observed endoscopically in 15 patients. However, radiography failed to detect other features noted at endoscopy (e.g., only 3/6 patients with proximal stenosis, 5/9 patients with concentric rings and none of 4 patients with small caliber esophagus). Eight of the 29 patients (20%) had a history of chronic heartburn. Twelve patients had been treated with a proton pump inhibitor and only 3 reported some improvement in the severity of dysphagia. CONCLUSIONS Relatively young age, a history of chronic dysphagia for solid food, and endoscopic detection of unique structural alterations atypical for GERD in an adult patient should prompt a suspicion of EE and subsequent biopsy confirmation. Acid reflux appears to have a secondary role in eosinophilic esophagitis. In an uncontrolled comparison, endoscopy was superior to barium contrast radiography for the diagnosis of eosinophilic esophagitis. The incidence of eosinophilic esophagitis in adults appears to be increasing.

Minimal hepatic encephalopathy is associated with motor vehicle crashes: the reality beyond the driving test.

Patients with minimal hepatic encephalopathy (MHE) have impaired driving skills, but association of MHE with motor vehicle crashes is unclear. Standard psychometric tests (SPT) or inhibitory control test (ICT) can be used to diagnose MHE. The aim was to determine the association of MHE with crashes and traffic violations over the preceding year and on 1‐year follow‐up. Patients with cirrhosis were diagnosed with MHE by ICT (MHEICT) and SPT (MHESPT). Self and department‐of‐transportation (DOT)‐reports were used to determine crashes and violations over the preceding year. Agreement between self and DOT‐reports was analyzed. Patients then underwent 1‐year follow‐up for crash/violation occurrence. Crashes in those with/without MHEICT and MHESPT were compared. 167 patients with cirrhosis had DOT‐reports, of which 120 also had self‐reports. A significantly higher proportion of MHEICT patients with cirrhosis experienced crashes in the preceding year compared to those without MHE by self‐report (17% vs 0.0%, P = 0.0004) and DOT‐reports (17% vs 3%, P = 0.004, relative risk: 5.77). SPT did not differentiate between those with/without crashes. A significantly higher proportion of patients with crashes had MHEICT compared to MHESPT, both self‐reported (100% vs 50%, P = 0.03) and DOT‐reported (89% vs 44%, P = 0.01). There was excellent agreement between self and DOT‐reports for crashes and violations (Kappa 0.90 and 0.80). 109 patients were followed prospectively. MHEICT patients had a significantly higher future crashes/violations compared to those without (22% vs 7%, P = 0.03) but MHESPT did not. MHEICT (Odds ratio: 4.51) and prior year crash/violation (Odds ratio: 2.96) were significantly associated with future crash/violation occurrence. Conclusion: Patients with cirrhosis and MHEICT have a significantly higher crash rate over the preceding year and on prospective follow‐up compared to patients without MHE. ICT, but not SPT performance is significantly associated with prior and future crashes and violations. There was an excellent agreement between self‐ and DOT‐reports. (HEPATOLOGY 2009.)

Probiotic Yogurt for the Treatment of Minimal Hepatic Encephalopathy

OBJECTIVES:Minimal hepatic encephalopathy (MHE), the preclinical stage of overt hepatic encephalopathy (OHE), is a significant condition affecting up to 60% of cirrhotics. All MHE therapies modify gut microflora, but consensus regarding MHE treatment and long-term adherence studies is lacking. The aim was to determine the effect of probiotic supplementation in the form of a food item, probiotic yogurt, on MHE reversal and adherence.METHODS:Nonalcoholic MHE cirrhotics (defined by a standard psychometric battery) were randomized with unblinded allocation to receive probiotic yogurt (with proven culture stability) or no treatment (no Rx) for 60 days in a 2:1 ratio. Quality of life (short form [SF]-36), adherence, venous ammonia, model of end-stage liver disease (MELD) scores, and inflammatory markers (tumor necrosis factor [TNF]-α, interleukin [IL]-6) were also measured. Outcomes were MHE reversal using blinded scoring, OHE development, and adherence.RESULTS:Twenty-five patients (17 yogurt, 8 no Rx; 84% Child class A) were enrolled. A significantly higher percentage of yogurt patients reversed MHE compared to no Rx patients (71% vs 0%, P= 0.003, intention-to-treat). Yogurt patients demonstrated a significant improvement in number connection test-A (NCT-A), block design test (BDT), and digit symbol test (DST) compared to baseline/no Rx group. Twenty-five percent of no Rx versus 0% of yogurt patients developed OHE during the trial. Eighty-eight percent of yogurt patients were adherent. No adverse effects or change in covariates were observed. All patients who completed the yogurt arm were agreeable to continue yogurt for 6 months if needed.CONCLUSIONS:This trial demonstrated a significant rate of MHE reversal and excellent adherence in cirrhotics after probiotic yogurt supplementation with potential for long-term adherence.

Persistence of Cognitive Impairment After Resolution of Overt Hepatic Encephalopathy

BACKGROUND & AIMS In patients with cirrhosis, hepatic encephalopathy (HE) has acute but reversible as well as chronic components. We investigated the extent of residual cognitive impairment following clinical resolution of overt HE (OHE). METHODS Cognitive function of cirrhotic patients was evaluated using psychometric tests (digit symbol, block design, and number connection [NCT-A and B]) and the inhibitory control test (ICT). Improvement (reduction) in ICT lures and first minus second halves (DeltaL(1-2)) were used to determine learning of response inhibition. Two cross-sectional studies (A and B) compared data from stable cirrhotic patients with or without prior OHE. We then prospectively assessed cognitive performance, before and after the first episode of OHE. RESULTS In study A (226 cirrhotic patients), 54 had experienced OHE, 120 had minimal HE, and 52 with no minimal HE. Despite normal mental status on lactulose after OHE, cirrhotic patients were cognitively impaired, based on results from all tests. Learning of response inhibition (DeltaL(1-2) > or =1) was evident in patients with minimal HE and no minimal HE but was lost after OHE. In study B (50 additional patients who developed > or =1 documented OHE episode during follow-up), the number of OHE hospitalizations correlated with severity of residual impairment, indicated by ICT lures (r = 0.5, P = .0001), digit symbol test (r = -0.39, P = .002), and number connection test-B (r = 0.33, P = .04). In the prospective study (59 cirrhotic patients without OHE), 15 developed OHE; ICT lure response worsened significantly after OHE (12 before vs 18 after, P = .0003), and learning of response inhibition was lost. The 44 patients who did not experience OHE did not have deteriorations in cognitive function in serial testing. CONCLUSIONS In cirrhosis, episodes of OHE are associated with persistent and cumulative deficits in working memory, response inhibition, and learning.

Association of Proton Pump Inhibitor Therapy With Spontaneous Bacterial Peritonitis in Cirrhotic Patients With Ascites

OBJECTIVES:Spontaneous bacterial peritonitis (SBP) is a frequent complication of cirrhosis. Bacterial contamination of ascites fluid leading to SBP is caused by bacterial translocation with subsequent bacteremia. Proton pump inhibitors (PPIs) suppress gastric acid secretion, allowing bacterial colonization of the upper gastrointestinal tract, and may predispose to bacterial overgrowth and translocation. The aim of this study was to determine whether PPI use in cirrhotics with ascites is associated with SBP.METHODS:A retrospective case–control study was performed. Seventy cirrhotics admitted with paracentesis-proven SBP between 2002 and 2007 were matched 1:1 (for age and Childs class) with comparable cirrhotics with ascites who were admitted for conditions other than SBP. We excluded patients on chronic antibiotic prophylaxis or with antecedent gastrointestinal bleeding. Outpatient PPI use at the time of admission was compared between groups, and the effect of covariates was analyzed.RESULTS:Patients with SBP had a significantly higher rate of prehospital PPI use (69%) compared with ascitic cirrhotics hospitalized without SBP (31%, P=0.0001). There was no significant difference in demographics, diabetes, etiology, or survival between groups. On multivariate analysis, PPI use was independently associated with SBP (odds ratio (OR) 4.31, confidence interval (CI) 1.34–11.7), and ascitic fluid protein was protective (OR 0.1, CI 0.03–0.25). In total, 47% of cirrhotic patients receiving PPI in this study had no documented indication for PPI treatment.CONCLUSIONS:PPI therapy is associated with SBP in patients with advanced cirrhosis. Prospective studies are needed to determine whether PPI avoidance can reduce the incidence of SBP and improve outcomes.

Inhibitory Control Test for the Diagnosis of Minimal Hepatic Encephalopathy

BACKGROUND & AIMS Minimal hepatic encephalopathy (MHE) is difficult to diagnose. The Inhibitory Control Test (ICT) measures response inhibition and has diagnosed MHE with 90% sensitivity and specificity in a selected population; high lure and low target rates indicated poor ICT performance. We studied the reliability and validity of ICT for MHE diagnosis. METHODS ICT was compared with a psychometric battery (standard psychometric tests [SPT]) for MHE diagnosis and overt hepatic encephalopathy (OHE) prediction. ICT was administered twice for test-retest reliability, before/after transvenous intrahepatic portosystemic shunting (TIPS), and before/after yogurt treatment. The time taken by 2 medical assistants (MA) to administer ICT was recorded and compared with that of a psychologist for cost analysis. RESULTS One hundred thirty-six cirrhotic patients and 116 age/education-matched controls were studied. ICT (>5 lures) had 88% sensitivity for MHE diagnosis with 0.902 area under the curve for receiver operating characteristic. MHE-positive patients had significantly higher ICT lures (11 vs 4, respectively, P = .0001) and lower targets (92% vs 97%, respectively, P = .0001) compared with MHE-negative patients. The test/retest reliability for ICT lures (n = 50, r = 0.90, P = .0001) was high. ICT and SPT were equivalent in predicting OHE (21%). ICT lures significantly worsened after TIPS (n = 10; 5 vs 9, respectively; P = .02) and improved after yogurt supplementation (n = 18, 10 vs 5, respectively; P = .002). The MAs were successfully trained to administer ICT; the time required for test administration and the associated costs were smaller for ICT than for SPT. CONCLUSIONS ICT is a sensitive, reliable, and valid test for MHE diagnosis that can be administered inexpensively by MAs.

Minimal hepatic encephalopathy: a vehicle for accidents and traffic violations.

OBJECTIVES: MHE patients have impairment on driving tests. However, it is unclear whether this impairment is restricted to the testing environment or is associated with increased traffic violations and/or motor vehicle accidents.METHODS: An anonymous driving history and driving behavior questionnaire (DBQ: self-scored, best score 104), coded according to MHE status, was sent to 200 cirrhotics without overt hepatic encephalopathy and 100 age/education-matched controls. The questionnaire inquired about demographics, alcohol/illegal drug use, and violations/accidents within 1 and 5 yr. The cirrhotics had been divided into those with MHE (MHE+), without MHE (MHE−), and those not tested for MHE because of psychoactive drug use, on a previous study.RESULTS: Cirrhotics versus controls had similar driving duration, alcohol/illegal drug use but significantly higher percentage with violations within both 1 and 5 yr (25% vs 4% [5 yr]), 13% vs 2% [(1 yr]), accidents (17% vs 4% [5 yr]), 9% vs 1% [1 yr]), and both (34% vs 7% [5 yr], 18% vs 3% [1 yr]). MHE+ cirrhotics had significantly higher percentage with violations (36% [5 yr], 21% [1 yr]), accidents (33% [5 yr]), 17% [1 yr]), and both (53% [5 yr], 33% [1 yr]) versus other cirrhotics. DBQ score was significantly lower in cirrhotics than controls (92 vs 99). Within cirrhotics, DBQ score was highest in MHE– versus other groups. MHE+ status was the only risk factor (odds ratios: 4.2–7.6) for violations and for accidents on multivariate logistic regression.CONCLUSIONS: Cirrhotics have a higher self-reported occurrence of violations and accidents compared to controls. MHE+ a is strong predictor for violations and accidents. Prospective studies investigating the effect of MHE treatment on violations and accidents are warranted.

Outcomes of Weekend Admissions for Upper Gastrointestinal Hemorrhage: A Nationwide Analysis

BACKGROUND & AIMS Previous studies have identified a weekend effect in outcomes of patients with various medical conditions suggesting worse outcomes for weekend admissions. The aim of our study was to analyze if weekend admissions for upper gastrointestinal hemorrhage (UGIH) have higher mortality and longer hospital stay compared with those admitted on weekdays, and to examine if this effect differs by hospital teaching status. METHODS This was a cross-sectional study using the Nationwide Inpatient Sample 2004. A total of 28,820 discharges with acute variceal hemorrhage (AVH) and 391,119 discharges with acute nonvariceal UGIH (NVUGIH) were identified through appropriate International Classification of Diseases, ninth edition codes. Admissions were considered to be weekend admissions if they were admitted between midnight on Friday through midnight on Sunday. In-hospital mortality, frequency, and timing of endoscopy were measured. RESULTS On multivariate analysis, NVUGIH patients admitted on weekends had higher adjusted in-hospital mortality (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.09-1.35) and were less likely to undergo early endoscopy within 1 day of hospitalization (OR, 0.64; 95% CI, 0.61-0.68). Weekend admission was not predictive of in-hospital mortality in patients with AVH (OR, 0.94; 95% CI, 0.75-1.18), but was associated with lower likelihood of early endoscopy in nonteaching hospitals (OR, 0.65; 95% CI, 0.51-0.82). Early endoscopy was associated with significantly shorter hospital stays (NVUGIH, -1.08 days; AVH, -2.35 days) and lower hospitalization charges (NVUGIH, -

Navigation skill impairment: Another dimension of the driving difficulties in minimal hepatic encephalopathy

1958; AVH, -

Infliximab retreatment in adults and children with Crohn's disease: risk factors for the development of delayed severe systemic reaction.

8870). CONCLUSIONS Patients with NVUGIH admitted on the weekend had higher mortality and lower rates of early endoscopy. Patient with AVH admitted to nonteaching hospitals also had lower utilization of early endoscopy, but no difference in survival. There is a need for research into identifying the reasons for the weekend effect.