HE In Patients Research Articles

Predicting hematoma expansion using machine learning: An exploratory analysis of the ATACH 2 trial

IntroductionHematoma expansion (HE) in patients with intracerebral hemorrhage (ICH) is a key predictor of poor prognosis and potentially amenable to treatment. This study aimed to build a classification model to predict HE in patients with ICH using deep learning algorithms without using advanced radiological features. MethodsData from the ATACH-2 trial (Antihypertensive Treatment of Acute Cerebral Hemorrhage) was utilized. Variables included in the models were chosen as per literature consensus on salient variables associated with HE. HE was defined as increase in either >33% or 6 mL in hematoma volume in the first 24 h. Multiple machine learning algorithms were employed using iterative feature selection and outcome balancing methods. 70% of patients were used for training and 30% for internal validation. We compared the ML models to a logistic regression model and calculated AUC, accuracy, sensitivity and specificity for the internal validation models respective models. ResultsAmong 1000 patients included in the ATACH-2 trial, 924 had the complete parameters which were included in the analytical cohort. The median [interquartile range (IQR)] initial hematoma volume was 9.93.mm3 [5.03–18.17] and 25.2% had HE. The best performing model across all feature selection groups and sampling cohorts was using an artificial neural network (ANN) for HE in the testing cohort with AUC 0.702 [95% CI, 0.631–0.774] with 8 hidden layer nodes The traditional logistic regression yielded AUC 0.658 [95% CI, 0.641–0.675]. All other models performed with less accuracy and lower AUC. Initial hematoma volume, time to initial CT head, and initial SBP emerged as most relevant variables across all best performing models. ConclusionWe developed multiple ML algorithms to predict HE with the ANN classifying the best without advanced radiographic features, although the AUC was only modestly better than other models. A larger, more heterogenous dataset is needed to further build and better generalize the models.

PHES scores have limited impact on the risk of overt HE in patients with minimal HE.

Minimal hepatic encephalopathy, defined by the portosystemic hepatic encephalopathy score (PHES), is associated with a higher risk of subsequent OHE. It remains unclear if there is a stepwise increase in OHE risk with worse PHES results. In this multicenter study, patients with minimal hepatic encephalopathy, as defined by abnormal PHES, were followed for OHE development. In all, 207 patients were included. There was no stepwise increase in OHE risk with worse PHES results. Abnormal PHES is associated with a higher OHE risk, but we found no stepwise increase in OHE risk with worse PHES results below the established cutoff.

Opioid use and risks in candidates and recipients of liver transplant.

Opioid use is extremely prevalent among patients with cirrhosis and those who received liver transplant (LT), despite concerns regarding opioid-related risks in this population. While there are many theoretical risks of opioids in patients with hepatic dysfunction, there is limited evidence on the effect of opioid use on clinical outcomes in cirrhosis and patients before and after LT specifically. As a result, there is significant center-level variability in opioid-related practices and policies. The existing data-largely based on retrospective observational studies-do suggest that opioids are associated with increased health resource utilization pre-LT and post-LT and that they may precipitate HE in patients with cirrhosis and increase the risk of graft loss and death after LT. The strongest predictor of opioid use after LT is opioid use before transplant; thus, a focus on safe opioid use in the pretransplant and peritransplant periods is essential for minimizing opioid-related harms. We describe 3 strategies to guide LT providers including (1) improved characterization of pain, mental health symptoms, and opioid and polysubstance use; (2) minimization of opioid prescriptions for those at highest risk of adverse events; and (3) safe prescribing strategies for those who do use opioids and for the management of opioid use disorder. Ultimately, our goal is to improve the quality of life and transplant outcomes among patients with cirrhosis and those who received LT, particularly those living with concurrent pain, mental health, and substance use disorders.

Comparison of 6 tests for diagnosing minimal hepatic encephalopathy and predicting clinical outcome: A prospective, observational study.

Current guidelines recommend the assessment for minimal HE in patients with liver cirrhosis. Various efforts were made to find tools that simplify the diagnosis. Here, we compare the 6 most frequently used tests for their validity and their predictive value for overt hepatic encephalopathy (oHE), rehospitalization, and death. One hundred thirty-two patients with cirrhosis underwent the Portosystemic Encephalopathy-Syndrome-Test yielding the psychometric hepatic encephalopathy score (PHES), Animal Naming Test (ANT), Critical Flicker Frequency (CFF), Inhibitory Control Test (ICT), EncephalApp (Stroop), and Continuous Reaction Time Test (CRT). Patients were monitored for 365 days regarding oHE development, rehospitalization, and death. Twenty-three patients showed clinical signs of HE grade 1-2 at baseline. Of the remaining 109 neurologically unimpaired patients, 35.8% had abnormal PHES and 44% abnormal CRT. Percentage of abnormal Stroop (79.8% vs. 52.3%), ANT (19.3% vs. 51.4%), ICT (28.4% vs. 36.7%), and CFF results (18.3% vs. 25.7%) changed significantly when adjusted norms were used for evaluation instead of fixed cutoffs. All test results correlated significantly with each other ( p <0.05), except for CFF. During follow-up, 24 patients developed oHE, 58 were readmitted to the hospital, and 20 died. Abnormal PHES results were linked to oHE development in the multivariable model. No other adjusted test demonstrated predictive value for any of the investigated endpoints. Where applicable, the diagnosis of minimal HE should be made based on adjusted norm values for the tests, exclusively. The minimal HE tests cannot be equated with one another and have an overall limited value in predicting clinical outcomes.

Association of non-contrast CT markers with long-term functional outcome in deep intracerebral hemorrhage.

Hematoma expansion (HE) is the most important therapeutic target during acute care of patients with intracerebral hemorrhage (ICH). Imaging biomarkers such as non-contrast CT (NCCT) markers have been associated with increasing risk for HE. The aim of the present study was to evaluate the influence of NCCT markers with functional long-term outcome and with HE in patients with deep (basal ganglia and thalamus) ICH who represent an important subgroup of patients at the highest risk for functional deterioration with HE due to the eloquence of the affected brain region. From our prospective institutional database, all patients maximally treated with deep ICH were included and retrospectively analyzed. NCCT markers were recorded at diagnostic imaging, ICH volume characteristics were volumetrically evaluated, and all patients received follow-up imaging within 0-48 h. We explored associations of NCCT makers with unfavorable functional outcome, defined as modified Rankin scale 4-6, after 12 months and with HE. Bias and confounding were addressed by multivariable regression modeling. In 322 patients with deep ICH, NCCT markers were distributed as follows: irregular shape: 69.6%, heterogenous density: 55.9%, hypodensities: 52.5%, island sign: 19.3%, black hole sign: 11.5%, and blend sign: 4.7%. Upon multivariable regression analyses, independent associations were documented with the functional outcome for irregular shape (aOR: 2.73, 95%CI: 1.42-5.22, p = 0.002), heterogenous density (aOR: 2.62, 95%CI: 1.40-4.90, p = 0.003) and island sign (aOR: 2.54, 95%CI: 1.05-6.14, p = 0.038), and with HE for heterogenous density (aOR: 5.01, 95%CI: 1.93-13.05, p = 0.001) and hypodensities (aOR: 3.75, 95%CI: 1.63-8.62, p = 0.002). NCCT markers are frequent in deep ICH patients and provide important clinical implications. Specifically, markers defined by diverging intra-hematomal densities provided associations with a 5-times higher risk for HE and a 2.5-times higher likelihood for unfavorable functional long-term outcome. Hence, these markers allow the identification of patients with deep ICH at high risk for clinical deterioration due to HE.

Predicting hepatic encephalopathy in patients with cirrhosis: A UK population-based study and validation of risk scores.

HE is a common neurologic complication in cirrhosis associated with substantial disease and economic burden. HE symptoms are nonspecific and there are limited ways of identifying patients with cirrhosis at high risk of later developing HE. A risk score was previously developed to identify patients at risk of developing HE in a predominately male US cohort. Here, we evaluated the performance of the HE risk scores in a UK cohort study. Health care records from Clinical Practice Research Datalink and linked Hospital Episode Statistics were used to select patients with cirrhosis who were diagnosed with HE, confirmed by a diagnosis code for HE or a rifaximin-α prescription. The index date was the date of incident cirrhosis. The study period was from January 2003 to June 2019. A total of 40,809 patients with cirrhosis were selected in the UK cohort, of whom 59% were male. A total of 1561 patients were diagnosed with HE. Applying the UK cohort to the baseline sensitivity risk cutoff (≥-11) from the US cohort provided a sensitivity of 92% and a negative predictive value of 99%. Within a longitudinal model, applying a sensitivity cutoff of ≥-3 to this cohort gave a sensitivity of 89% and a negative predictive value of 99%. Using data from the UK, the previously developed HE risk scores were found to be reliable for selecting those most likely to progress to HE in patients with liver cirrhosis. Despite the HE risk scores originally being estimated using the data from a predominately male US cohort, the scores were validated and found to be generalizable to female patients.

Association of preoperative IL-6 levels with overt HE in patients with cirrhosis after TIPS.

HE is a common and dangerous complication after TIPS. The relationship between IL-6 levels and overt HE (OHE) after TIPS is rarely reported.We aimed to explore the relationship between the preoperative serum IL-6 levels and OHE risk after TIPS, and to evaluate its value in predicting the OHE risk. This prospective cohort study included 125 participants with cirrhosis who received TIPS. Logistics regression analyses were performed to explore the relationship between IL-6 and OHE risk, and the receiver operating characteristic analysis was used to compare the predictive power of IL-6 and other indexes. Among 125 participants, 44 (35.2%) participants developed OHE after TIPS. Logistics regression showed preoperative IL-6 was associated with a higher OHE risk after TIPS in different models (all p < 0.05). Participants with IL-6 > 10.5pg/mL had a higher cumulative incidence of OHE after TIPS than those with IL-6 ≤ 10.5pg/mL (log-rank = 0.0124). The predictive power of IL-6 (AUC = 0.83) for the OHE risk after TIPS was higher than that of other indexes. Age (RR = 1.069, p = 0.002) and IL-6 (RR = 1.154, p < 0.001) were independent risk factors for OHE after TIPS. IL-6 was also a risk factor for the occurrence of coma in patients with OHE (RR = 1.051, p = 0.019). Preoperative serum IL-6 levels are closely related to the occurrence of OHE in patients with cirrhosis after TIPS. Patients with cirrhosis with high serum IL-6 levels following TIPS were at a higher risk of developing severe HE.

A non-contrast computed tomography-based radiomics nomogram for the prediction of hematoma expansion in patients with deep ganglionic intracerebral hemorrhage.

Background and purposeHematoma expansion (HE) is a critical event following acute intracerebral hemorrhage (ICH). We aimed to construct a non-contrast computed tomography (NCCT) model combining clinical characteristics, radiological signs, and radiomics features to predict HE in patients with spontaneous ICH and to develop a nomogram to assess the risk of early HE.Materials and methodsWe retrospectively reviewed 388 patients with ICH who underwent initial NCCT within 6 h after onset and follow-up CT within 24 h after initial NCCT, between January 2015 and December 2021. Using the LASSO algorithm or stepwise logistic regression analysis, five models (clinical model, radiological model, clinical-radiological model, radiomics model, and combined model) were developed to predict HE in the training cohort (n = 235) and independently verified in the test cohort (n = 153). The Akaike information criterion (AIC) and the likelihood ratio test (LRT) were used for comparing the goodness of fit of the five models, and the AUC was used to evaluate their ability in discriminating HE. A nomogram was developed based on the model with the best performance.ResultsThe combined model (AIC = 202.599, χ2 = 80.6) was the best fitting model with the lowest AIC and the highest LRT chi-square value compared to the clinical model (AIC = 232.263, χ2 = 46.940), radiological model (AIC = 227.932, χ2 = 51.270), clinical-radiological model (AIC = 212.711, χ2 = 55.490) or radiomics model (AIC = 217.647, χ2 = 57.550). In both cohorts, the nomogram derived from the combined model showed satisfactory discrimination and calibration for predicting HE (AUC = 0.900, sensitivity = 83.87%; AUC = 0.850, sensitivity = 80.10%, respectively).ConclusionThe NCCT-based model combining clinical characteristics, radiological signs, and radiomics features could efficiently discriminate early HE, and the nomogram derived from the combined model, as a non-invasive tool, exhibited satisfactory performance in stratifying HE risks.

Concurrent large spontaneous portosystemic shunt embolization for the prevention of overt hepatic encephalopathy after TIPS: A randomized controlled trial.

Large spontaneous portosystemic shunt (SPSS) is associated with increased risk of HE in patients undergoing transjugular intrahepatic portosystemic shunt (TIPS). This study aimed to evaluate whether prophylactic embolization of large SPSS at the time of TIPS creation could reduce the incidence of post-TIPS HE in patients with cirrhosis and variceal bleeding. From June 2014 to August 2017, 56 patients with cirrhosis and large SPSS planning to undergo TIPS for the prevention of variceal bleeding were randomly assigned (1:1) to receive TIPS alone (TIPS group, n=29) or TIPS plus simultaneous SPSS embolization (TIPS+E group, n=27). The primary endpoint was overt HE. TIPS placement and SPSS embolization was successful in all patients. During a median follow-up of 24 months, the primary endpoint was met in 15 patients (51.7%) in the TIPS group and six patients (22.2%) in the TIPS+E group (p=0.045). The 2-year cumulative incidence of overt HE was significantly lower in the TIPS+E group compared with the TIPS group (21.2% vs. 48.3%; HR, 0.38; 95% CI, 0.15-0.97; p=0.043). The 2-year incidence of recurrent bleeding (TIPS+E vs. TIPS, 15.4% vs. 25.1%; p=0.522), shunt dysfunction (12.3% vs. 18.6%, p=0.593), death (15.0% vs. 6.9%, p=0.352), and other adverse events was not significantly different between the two groups. In patients with cirrhosis treated with TIPS for variceal bleeding, concurrent large SPSS embolization reduced the risk for overt HE without increasing other complications. Concurrent large SPSS embolization should therefore be considered for prophylaxis of post-TIPS HE.

Predicting in-hospital mortality of cirrhotic patients hospitalized with hepatic encephalopathy

BackgroundHepatic encephalopathy (HE) is a serious condition associated with high rates of mortality. Many scoring systems are used to predict the outcome of HE in patients admitted to the intensive care unit (ICU). The most used scores are Child-Turcotte-Pugh (CTP), Model for End-stage Liver Disease (MELD), Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA), and Acute Physiology and Chronic Health Evaluation II (APACHE II). These scores were thoroughly investigated in HE associated with acute liver failure (type A). In the present study, we aimed to evaluate the prognostic value of these scores in patients with HE on a background of liver cirrhosis (type C). Two hundred cirrhotic patients hospitalized with HE were included in the study. Diagnosis and classification of HE were based on the West Haven criteria. APACHE II, CLIF-SOFA, MELD, MELD-Na, and CTP scores were calculated for all patients within the first 24 h after admission. According to survival outcomes, patients were categorized into either improved or deceased. Demographic, clinical, and laboratory data as well as prognostic scores were compared in both deceased and improved groups. The receiver operating characteristic (ROC) curve was plotted, and the area under the ROC curve (AUROC) was calculated for each score. Backward logistic regression analysis was used to identify the predictors of mortality.Results60.5% of patients were males. The mean age was 61.09 ± 8.94 years. The main precipitating factors of HE was infections predominantly spontaneous bacterial peritonitis (n = 108, 54.0%) followed by variceal bleeding (n = 39, 19.5%). All scores were significantly higher in the deceased patients. AUROC were 0.734 (CI95% 0.666–0.803), 0.717 (CI95% 0.647–0.787), 0.663 (CI95% 0.589–0.738), 0.626 (CI95% 0.549–0.704), and 0.609 (CI95% 0.531–0.686) for CLIF-SOFA, MELD-Na, MELD, APACHE II, and CTP scores, respectively. MELD, MELD-Na, and CLIF-SOFA scores were the independent predictors of mortality. Among these scores, CLIF-SOFA was the strongest independent predictor of mortality (OR = 1.142, CI95% = 0.888–1.467, p = 0.001).ConclusionsCLIF-SOFA score was superior to other prognostic scores in predicting mortality in hospitalized patients with HE type C.

Using machine learning methods to predict hepatic encephalopathy in cirrhotic patients with unbalanced data

ObjectiveHepatic encephalopathy (HE) is among the most common complications of cirrhosis. Data for cirrhosis with HE is typically unbalanced. Traditional statistical methods and machine learning algorithms thus cannot identify a few classes. In this paper, we use machine learning algorithms to construct a risk prediction model for liver cirrhosis complicated by HE to improve the efficiency of its prediction. MethodWe collected medical data from 1,256 patients with cirrhosis and performed preprocessing to extract 81 features from these irregular data. To predict HE in cirrhotic patients, we compared several classification methods: logistic regression, weighted random forest (WRF), SVM, and weighted SVM (WSVM). We also used an additional 722 patients with cirrhosis for external validation of the model. ResultsThe WRF, WSVM, and logistic regression models exhibited better recognition ability for patients with HE than traditional machine learning models (sensitivity> 0.70), but their ability to identify patients with uncomplicated HE was slightly lower (specificity approximately 85%). The comprehensive evaluation index of the traditional model was higher than those of other models (G-means> 0.80 and F-measure> 0.40). For the WRF, the G-means (0.82), F-measure (0.46), and AUC (0.82) were superior to those of the logistic regression and WSVM models, which means that it can better predict the incidence of HE in patients. ConclusionThe WRF model is more suitable for the classification of unbalanced medical data and can be used to construct a risk prediction and evaluation system for liver cirrhosis complicated with HE. The probabilistic prediction models of WRF can help clinicians identify high-risk patients with HE.

Pathomechanisms in hepatic encephalopathy.

Hepatic encephalopathy (HE) is a frequent neuropsychiatric complication in patients with acute or chronic liver failure. Symptoms of HE in particular include disturbances of sensory and motor functions and cognition. HE is triggered by heterogeneous factors such as ammonia being a main toxin, benzodiazepines, proinflammatory cytokines and hyponatremia. HE in patients with liver cirrhosis is triggered by a low-grade cerebral edema and cerebral oxidative/nitrosative stress which bring about a number of functionally relevant alterations including posttranslational protein modifications, oxidation of RNA, gene expression changes and senescence. These alterations are suggested to impair astrocyte/neuronal functions and communication. On the system level, a global slowing of oscillatory brain activity and networks can be observed paralleling behavioral perceptual and motor impairments. Moreover, these changes are related to increased cerebral ammonia, alterations in neurometabolite and neurotransmitter concentrations and cortical excitability in HE patients.

Black Hole Sign on Noncontrast Computed Tomography in Predicting Hematoma Expansion in Patients with Intracerebral Hemorrhage: A Meta-analysis.

Black hole sign represents a novel imaging marker for predicting hematoma expansion (HE) in patients with intracerebral hemorrhage (ICH). Several previous studies have reported the accuracy of black hole sign in predicting HE, but the accuracy was variable. We performed a meta-analysis to systematically assess the accuracy of black hole sign in predicting HE in patients with ICH. A systematic search was performed to identify relevant English and Chinese articles (from inception to January 2019). All studies on the accuracy of black hole sign in predicting HE in patients with ICH were included. Pooled sensitivity, specificity, and positive and negative likelihood ratios were calculated. Pooling was conducted using the bivariate generalized linear mixed model. Forest plots and a summary receiver operator characteristic plot were generated. We used I² to test heterogeneity and investigated the source of heterogeneity by meta-regression. Publication bias was assessed by Deeks' funnel plot asymmetry test. A total of 6 studies with 1876 patients were included in this meta-analysis. The pooled sensitivity, specificity, and positive and negative likelihood ratios of black hole sign for predicting HE were 0.30, 0.93, 4.00 and 0.75, respectively. The area under the curve (AUC) was 0.83. The studies had substantial heterogeneity (I²=89.00%, 95% CI 78.00-100.00). Low risk of publication bias was detected. Black hole sign is a useful imaging marker with high specificity in predicting hematoma expansion in patients with intracerebral hemorrhage.

Early hematoma expansion in primary intracerebral hemorrhage: incidence and predictors

BackgroundHematoma expansion (HE) is the leading cause of early neurological deterioration, poor functional outcome, and increased mortality in patients with spontaneous intracerebral hemorrhage (S-ICH). The study aimed to estimate the risks and predictors of early HE in patients with S-ICH and the effect of this HE on patient’s survival and functional outcome.MethodsThis study was carried out on 72 patients with S-ICH submitted to baseline non-contrast brain CT (NCCT) and CT angiography for determination of hematoma site, size, border irregularity, blend sign, and spot sign score (SSS). Rescan was done 48 h after stroke onset or on clinical deterioration to resize the HV and diagnose HE. Modified Rankin Scale (MRS) was done 3 months after stroke onset to assess the effect of HE on patients’ physical dependence.ResultsHE occurred in 28/72 (38.9%) of included patients. Risks of HE included old age, smoking, elevated baseline mean arterial blood pressure, and high admission modified National Institute of Health stroke scale. NCCT predictors of HE included large volume, irregular border, and presence of blend sign. The presence of spot sign in early CTA is more accurate than NCCT predictors with 54%, 91%, 79%, and 75% for sensitivity, specificity, positive predictive value, and negative predictive value, respectively.ConclusionsHE is a major cause of early clinical deterioration, increased mortality, and poor functional outcome. Early CTA for detection of spot sign is indicated in patients with large volume, irregular border, and/or blend sign in NCCT.

Serial assessment of hepatic encephalopathy in patients hospitalised for acute decompensation of cirrhosis

Introduction and aimHepatic encephalopathy (HE) is a frequent complication of cirrhosis, but the clinical and prognostic significance of the progression of mental status in hospitalised cirrhotics is unknown. We aimed to investigate the prognostic significance of serial evaluation of HE in patients hospitalised for acute decompensation (AD) of cirrhosis. Materials and methodsPatients (n=293) were evaluated for HE (West-Haven criteria) at admission and at day-3 and classified in two groups: (1) Absent or improved HE: HE absent at admission and at day-3, or any improvement at day-3; (2) Unfavourable progression: Development of HE or HE present at admission and stable/worse at day-3. ResultsUnfavourable progression of HE was observed in 31% of patients and it was independently associated with previous HE, Child–Pugh C and acute-on-chronic liver failure (ACLF). MELD score and unfavourable progression of HE were independently associated with 90-day mortality. The 90-day Kaplan–Meier survival probability was 91% in patients with MELD<18 and absent or improved HE and only 31% in subjects with both MELD≥18 and unfavourable progression of HE. Unfavourable progression of HE was also related to lower survival in patients with or without ACLF. Worsening of GCS at day-3 was observed in 11% of the sample and was related with significantly high mortality (69% vs. 27%, P<0.001). ConclusionAmong cirrhotics hospitalised for AD, unfavourable progression of HE was associated with high short-term mortality and therefore can be used for prognostication and to individualise clinical care.

A genetic variant in the promoter of phosphate-activated glutaminase is associated with hepatic encephalopathy.

Hepatic encephalopathy (HE) is a serious complication of liver cirrhosis. Recently, a microsatellite in the promoter region of the phosphate-activated glutaminase (GLS) gene was associated with the risk of HE. The aim of the present study was to investigate, using the critical flicker frequency (CFF) test, whether the described GLS variant increases the risk of developing HE in patients with cirrhosis. We recruited 158 patients (66% men; mean age 59years, range 23-86) with liver cirrhosis. Mean model for end-stage liver disease score was 13.8 (range 5-35); 48% of patients presented with Child-Pugh score B or C. The presence and severity of HE were determined by the CFF test, with frequencies ≤39Hz denoting cases. GLS variants were genotyped by sequencing the microsatellite in the promoter region and were classified as short, long or short-long forms (depending on the length of the macrosatellite alleles). In total, 53% of patients had abnormal CFF results (i.e. ≤39Hz; range for entire cohort 26-57). The GLS microsatellite distribution amongst patients was short form (20%), long form (32%) and short-long form (48%) and was consistent with Hardy-Weinberg equilibrium. CFF values differed significantly between groups (P=0.043). Carriers of the GLS long microsatellite had a significantly higher risk of HE according to multivariate analyses (odds ratio3.23, 95%confidence interval1.46-7.13, P=0.004). CFF results were significantly lower amongst carriers of the GLS long microsatellite. Our findings support the role of the GLS long microsatellite in the development of HE; this could be important for identifying susceptible patients and for the prevention of this condition.

Challenges in diagnosing hepatic encephalopathy.

The term "hepatic encephalopathy" (HE) covers the neuropsychiatric syndrome associated with acute, chronic and acute-on-chronic liver disease (CLD). This paper deals with clinical features and diagnosis of HE in patients with liver cirrhosis and portal hypertension or porto-systemic shunts. The possible impact of concomitant disorders and the cirrhosis underlying liver disease upon brain function is described emphasizing the need of a detailed diagnostic work up of every individual case before diagnosing HE. Currently used methods for diagnosing minimal or covert hepatic encephalopathy are compared with regard to their sensitivity and specificity for diagnosing HE against the background of a multitude of concomitant disorders and diseases that could contribute to brain dysfunction.

24 SPONTANEOUS BACTERIAL PERITONITIS—A CLINICAL STUDY IN CIRRHOTIC PATIENTS WITH ASCITES

A b st ra ct s Aim: To study the effects of lactulose and probiotics for secondary prophylaxis of HE. Method: Consecutive cirrhotic patients who recovered from HE were randomized to receive lactulose (Group-L, 30 mL/3 times/day), probiotics (Group-P) three capsules/ day containing 112.5 billion viable lyophilized bacteria per capsule and no therapy (Group-N). All patients were assessed by psychometry (number connection test [NCT-A, B], figure connection test if illiterate [FCT-A, B], digit symbol test (DST), and block design test [BDT]), critical flicker frequency test (CFF) and arterial ammonia at inclusion, and patients were followed up monthly. Development of overt HE was the primary end-point, according to West-Haven criteria or a follow-up of 12 months. Result: Of 360 who recovered, 235 (65.2%) met the inclusion criteria (Group-L, n = 80; Group-P, n = 77 and Group-N, n = 78). Thirty-eight patients (16.1%) were lost to followup. Seventy-seven patients developed HE (Group-L, n = 18; Group-P, n = 22 and Group-N, n = 37). There was significant difference between Group-L vs Group-N (P = 0.001) and between Group-P vs Group-N (P = 0.02) while no difference between Group-L vs Group-P group (P = 0.349). Readmission rate due to causes other than HE (Group-L:Group-P: Group-N, 19:21:28 P = .0.134) and deaths (Group-L: Group-P:Group-N, 13:11:16 P = 0.56) in three groups were similar. There was a high prevalence of abnormal psychometric test results (NCT-A, 71.5%; NCT-B, 69.2%; DST, 76.9%; and BDT, 85.2%). The CFF was < 38 Hz in 118 patients (50.2%). On multivariate analysis, recurrence of overt HE was significantly associated with two or more abnormal psychometric tests and arterial ammonia after the recovery of an episode of HE. Conclusion: Lactulose and probiotics are effective for secondary prophylaxis of HE in patients with cirrhosis.

High estradiol levels (over 2000 pg/ml) in the day of hCG administration are associated with lower blastocysts rates but only in own oocytes and not in donated oocytes cycles

OBJECTIVE: High levels of estradiol (HE) after controlled ovarian hyperstimulation (COH) and the consequences on the outcome of in vitro fertilization (IVF) treatments remain controversial, mainly when high numbers are picked-up and the risk of suffering syndrome of ovarian hiperstimulation is present. The current study was conducted in our standard IVF cycles (SC) and the oocyte donation (OD) program, in order to depict if the HE in patients and donors after COH affects blastocyst rate formation (BR).

Treatment of Acute Intracerebral Hemorrhage with ε-Aminocaproic Acid: A Pilot Study

Up to 40% of primary intracerebral hemorrhages (ICHs) expand within the first 24 hours (natural history). The authors aimed to study the safety and preliminary efficacy of epsilon-aminocaproic acid (EACA) in halting ICH enlargement. Consecutive patients with hematoma volumes ranging from 5 to 80 mL were recruited within 12 hours of ICH onset. A total of 5 g EACA was infused during 1 hour and then 1 g/hour for 23 hours. Hematoma volume was compared on baseline, and 24-48-hour brain imaging. Consecutive untreated patients underwent the same imaging protocol. Three of the first five patients treated had HE>33% of their baseline volume. HE occurred in two of the nine untreated patients. The 80% confidence interval for HE in the treated patients was 32-88%. No thrombotic or other serious adverse events were attributed to EACA. It is unlikely that the rate of HE in patients given EACA within 12 hours of ICH is less than the natural history rate, although this treatment appears to be safe.