The Natural History of Severe Acute Liver Injury.

OBJECTIVES: Acute liver failure (ALF) is classically defined by coagulopathy and hepatic encephalopathy (HE); however, acute liver injury (ALI), i.e., severe acute hepatocyte necrosis without HE, has not been carefully defined nor studied. Our aim is to describe the clinical course of specifically defined ALI, including the risk and clinical predictors of poor outcomes, namely progression to ALF, the need for liver transplantation (LT) and death. METHODS: 386 subjects prospectively enrolled in the Acute Liver Failure Study Group registry between 1 September 2008 through 25 October 2013, met criteria for ALI: International Normalized Ratio (INR)≥2.0 and alanine aminotransferase (ALT)≥10 × elevated (irrespective of bilirubin level) for acetaminophen (N-acetyl-p-aminophenol, APAP) ALI, or INR≥2.0, ALT≥10x elevated, and bilirubin≥3.0 mg/dl for non-APAP ALI, both groups without any discernible HE. Subjects who progressed to poor outcomes (ALF, death, LT) were compared, by univariate analysis, with those who recovered. A model to predict poor outcome was developed using the random forest (RF) procedure. RESULTS: Progression to a poor outcome occurred in 90/386 (23%), primarily in non-APAP (71/179, 40%) vs. only 14/194 (7.2%) in APAP patients comprising 52% of all cases (13 cases did not have an etiology assigned; 5 of whom had a poor outcome). Of 82 variables entered into the RF procedure: etiology, bilirubin, INR, APAP level and duration of jaundice were the most predictive of progression to ALF, LT, or death. CONCLUSIONS: A majority of ALI cases are due to APAP, 93% of whom will improve rapidly and fully recover, while non-APAP patients have a far greater risk of poor outcome and should be targeted for early referral to a liver transplant center.

Randomized controlled trial of EUS-guided fine needle aspiration techniques for the detection of malignant lymphadenopathy.

BACKGROUND: EUS-guided fine needle aspiration (EUS-FNA) is a highly accurate method of detecting malignant lymphadenopathy. The optimal methods for performing EUS-FNA to maximize sensitivity and to minimize the number of needle passes necessary are unknown. This is a report of the results of a prospective randomized controlled trial to determine the effect of suction, the site of FNA (edge or center of lymph node), and the method of preparation of cytologic specimens on accuracy, number of needle passes needed, and specimen quality. METHODS: Consecutive patients with lymphadenopathy detected by EUS underwent FNA. Each lymph node was sampled with or without suction and from the edge or center in a 2 x 2 factorial design. The samples were expressed onto slides for cytology, and the residual material in the needle was analyzed by the cytospin-cellblock technique. Each aspirate was individually characterized for a diagnosis of malignancy, cellularity, and bloodiness. RESULTS: Forty-three patients with a total of 46 lymph nodes were evaluated. The final lymph node diagnosis was benign in 22 (48%), "suspicious for malignancy" in 6 (13%), and malignant in 18 (39%). The use of suction was associated with an increase in the cellularity of the specimen, but did not improve the likelihood of obtaining a correct diagnosis (OR 1.52: 95% CI [0.81, 2.85]). Samples obtained with suction were of worse quality because of excessive bloodiness (OR 4.7: 95% CI [1.99, 11.24]). Aspiration from the edge of the lymph node (compared with the center) did not increase the likelihood of a correct diagnosis (OR 1.16: 95% CI [0.42, 3.21]). For 78% of malignant lymph nodes, the correct diagnosis was obtained on the first needle pass and for 100% by the third pass. Cytospin-cellblock methods did not add any additional diagnostic information compared with direct smear cytology. CONCLUSIONS: The traditional method of applying suction during EUS-FNA does not improve diagnostic accuracy and worsens specimen bloodiness compared with FNA without suction. The site of FNA within the lymph node does not affect accuracy. When EUS-FNA is necessary, our recommendation is up to 3 FNAs without suction from the most convenient and safe location within abnormal-appearing lymph nodes.

Age and alarm symptoms do not predict endoscopic findings among patients with dyspepsia: a multicentre database study.

INTRODUCTION: Symptoms of dyspepsia are common but most patients do not have major upper gastrointestinal pathology. Endoscopy is recommended for dyspeptic patients over the age of 45, or those with certain "alarm" symptoms. We have evaluated the effectiveness of age and "alarm" symptoms for predicting major endoscopic findings in six practising endoscopy centres. METHODS: Clinical variables of consecutive patients with dyspepsia symptoms undergoing upper endoscopy examinations were recorded using a common endoscopy database. Patients who had no previous upper endoscopy or barium radiography were included. Stepwise multivariate logistic regression was used to identify predictors of endoscopic findings. The accuracy of these for predicting endoscopic findings was evaluated with receiver operating characteristic analysis. The sensitivity and specificity of age thresholds from 30 to 70 years were evaluated. RESULTS: Major pathology (tumour, ulcer, or stricture) was found at endoscopy in 787/3815 (21%) patients with dyspepsia. Age, male sex, bleeding, and anaemia were found to be significant but weak independent predictors of endoscopic findings. A multivariate prediction rule based on these factors had poor predictive accuracy (c statistic=0.62). Using a simplified prediction rule of age > or =45 years or the presence of any "alarm" symptom, sensitivity was 87% and specificity was 26%. Increasing or decreasing the age cut off did not significantly improve the predictive accuracy. CONCLUSIONS: Age and the presence of "alarm" symptoms are not effective predictors of endoscopic findings among patients with dyspepsia. Better clinical prediction strategies are needed to identify patients with significant upper gastrointestinal pathology.

The reliability of EUS for the diagnosis of chronic pancreatitis: interobserver agreement among experienced endosonographers.

BACKGROUND: Endoscopic ultrasound (EUS) is a minimally invasive, low risk method of diagnosis for chronic pancreatitis (CP). The degree to which endosonographers agree on the features and diagnosis of CP is unknown. For EUS to be considered an accurate test for CP, there must be good interobserver agreement. METHODS: Forty-five pancreatic EUS examinations were videotaped by 3 experienced endosonographers. Examinations from 33 patients with suspected CP based on typical symptoms, as well as 12 control patients without suspected CP, were included. Eleven experienced endosonographers ("experts") who were blinded to clinical information independently evaluated all videotaped examinations for the presence of CP and the following 9 validated features of CP: echogenic foci, strands, lobularity, cysts, stones, duct dilatation, duct irregularity, hyperechoic duct margins, and visible side branches. The experts also ranked (most to least) which features they believed to be the most indicative of CP. Interobserver agreement was expressed as the kappa (kappa) statistic. RESULTS: There was moderately good overall agreement for the final diagnosis of CP (kappa = 0.45). Agreement was good for individual features of duct dilatation (kappa = 0.6) and lobularity (kappa = 0.51) but poor for the other 7 features (kappa < 0.4). The expert panel had consensus or near consensus agreement (greater than 90%) on 206 of 450 (46%) individual EUS features including 22 of 45 diagnoses of CP. Agreement on the final diagnosis of CP was moderately good for those trained in third tier fellowships (kappa = 0.42 +/- 0.03) and those with more than 1100 lifetime pancreatic EUS examinations (kappa = 0.46 +/- 0.05). The presence of stones was regarded as the most predictive feature of CP by all endosonographers, followed by visible side branches, cysts, lobularity, irregular main pancreatic duct, hyperechoic foci, hyperechoic strands, main pancreatic duct dilatation, and main duct hyperechoic margins. The most common diagnostic criterion for the diagnosis of CP was the total number of features (median 4 or greater, range 3 or greater to 5 or greater). CONCLUSIONS: EUS is a reliable method for the diagnosis of chronic pancreatitis with good interobserver agreement among experienced endosonographers. Agreement on the EUS diagnosis of chronic pancreatitis is comparable to other commonly used endoscopic procedures such as bleeding ulcer stigmata and computed tomography of the brain for stroke localization and better than the physical diagnosis of heart sounds.

Sonographic prediction of twin birth weight discordance.

OBJECTIVE: To assess the accuracy of sonographic prediction of clinically significant twin birth weight discordance (25% or greater) and to determine whether this accuracy is affected by defined fetal and maternal variables. METHODS: Using an established database, we reviewed 338 twin gestations delivered over 10 years as a retrospective cohort. Estimation of fetal weight was calculated by applying the Hadlock formula using composite fetal biometry. Intertwin weight discordance was calculated as the difference in the estimated or actual twin weights (A-B) divided by the weight of the larger twin and was expressed as a percentage. Statistical evaluation included validity (sensitivity, specificity, and predictive values) and reliability assessment of ultrasonographic measurements (intraclass correlation coefficients). Multivariable analysis was performed. RESULTS: Of 338 twin gestations, 192 (57%) twin pairs met inclusion criteria. Sonographic prediction of actual intertwin birth weight discordance of 25% or greater had a sensitivity of 55%, specificity of 97%, positive predictive value of 82%, and negative predictive value of 91%. The reliability of estimating intertwin birth weight discordance by ultrasonography was moderately high (intraclass correlation coefficient =.700; 95% confidence interval [CI].620,.765). Multivariable analysis revealed no significant effects of individual maternal or fetal factors on the accuracy of ultrasonographic prediction of intertwin birth weight discordance. CONCLUSION: Sonographic prediction of actual intertwin birth weight discordance of 25% or greater within 16 days of delivery appears to be a valid and reliable method for clinical use. Predictive accuracy is independent of other identifiable maternal or fetal variables.

Validation of virtual colonoscopy in the detection of colorectal polyps and masses: rationale for proper study design.

BACKGROUND: Colorectal cancer, the second-leading cause of cancer-related mortality, is a preventable malignancy in many cases. Despite the availability of several screening modalities, compliance with screening recommendations remains unacceptably low. Virtual colonoscopy is a novel, minimally-invasive technique with the potential to increase colorectal cancer screening rates, but its effectiveness must first be validated. Published studies comparing virtual colonoscopy to conventional colonoscopy have reported varying results. These discrepancies may be attributed to differences in bowel preparation and scanning techniques, as well as errors in endoscopic lesion measurement, endoscopic colonic segmental localization, and the ability of conventional colonoscopy to actually detect lesions. These methodological issues can affect scientific results and ultimately affect the public's perception of this emerging technique. AIM: The goal of this report is to expose existing methodological shortcomings and propose solutions incorporated in this study design. This article describes the rationale, study design, and outcome definitions of a single-center, blinded, direct comparative trial aiming at assessing the ability of virtual colonoscopy to detect colorectal polyps and masses relative to the criterion standard, conventional colonoscopy. DESIGN FEATURES: Bowel preparation was standardized using oral sodium phosphate lavage, orally administered iodinated contrast, and controlled colonic insufflation. Segmental unblinding allowed a second-look when results were discrepant and polyp matching was performed using an algorithm based on segmental localization and lesion size determination. CONCLUSIONS: This methodology could be applied to other studies assessing the accuracy of virtual colonoscopy in order to have uniformity of results.

Endoscopic ultrasound-guided fine needle aspiration for staging patients with carcinoma of the lung.

BACKGROUND: Endoscopic ultrasound (EUS)-guided fine needle aspiration is a safe, cost-effective procedure that can confirm the presence of mediastinal lymph node metastases and mediastinal tumor invasion. We studied the accuracy of EUS in a large population of lung cancer patients with and without enlarged mediastinal lymph nodes on computed tomographic (CT) scan. METHODS: From 1996 to 2000 all patients referred to our institution with lung tumors and no proven distant metastases were considered for EUS and surgical staging. Patients had endoscopic ultrasound with fine needle aspiration of abnormal appearing mediastinal lymph nodes and evaluation for mediastinal invasion of tumor (stage III or IV disease). Patients without confirmed stage III or IV disease had surgical staging. RESULTS: Two hundred seventy-seven patients met the inclusion criteria, including 121 who had EUS. Endoscopic ultrasound and fine needle aspiration detected stage III or IV disease in 85 of 121 (70%). Among patients with enlarged lymph nodes on CT, 75 of 97 (77%) had stage III or IV disease detected by EUS. Among a small cohort of patients without enlarged mediastinal lymph nodes on CT, 10 of 24 (42%) had stage III or IV disease detected by EUS. For mediastinal lymph nodes only, the sensitivity of endoscopic ultrasound and CT was 87%. The specificity of EUS (100%) was superior to that of CT (32%) (p < 0.001). CONCLUSIONS: Endoscopic ultrasound with fine needle aspiration identified and histologically confirmed mediastinal disease in more than two thirds of patients with carcinoma of the lung who have abnormal mediastinal CT scans. Although mediastinal disease was more likely in patients with an abnormal mediastinal CT, EUS also detected mediastinal disease in more than one third of patients with a normal mediastinal CT and deserves further study. Endoscopic ultrasound should be considered a first line method of presurgical evaluation of patients with tumors of the lung.

Determining the clinical efficacy and cost savings of successful external cephalic version.

OBJECTIVE: The aim of this study was to determine predictors of successful external cephalic version and to calculate the associated cost savings achieved with success. STUDY DESIGN: A retrospective study of 203 women with singleton gestations who underwent external cephalic version was performed. Descriptive, univariate, and multivariate analyses were performed on patient-specific risk data to predict successful version. National claims data were used for the cost simulation. RESULTS: Higher parity (p = 0.02), transverse-oblique presentation (p = 0.001), posterior placenta (p = 0.001), and a longer duration of pregnancy (p = 0.001) significantly increased the likelihood of a successful version. Heavier maternal weight was negatively associated with successful version (p = 0.05). The cost simulation revealed an average savings of $2462 for each successful version. CONCLUSION: This study identifies clinical variables associated with an increased external cephalic version success rate. If, in fact, successful external cephalic version reduces both maternal and fetal morbidity associated with cesarean delivery and, as demonstrated in this analysis, the costs associated with the delivery, then greater effort should be made to maximize the success rate of external cephalic version.