Frontal assessment battery: A tool for screening minimal hepatic encephalopathy?

AIM To apply the Frontal Assessment Battery to cirrhotic patients with or without overt hepatic encephalopathy(OHE) and controls. METHODS The frontal assessment battery(FAB) was applied to 87 patients with liver cirrhosis(16 with and 71 without OHE) and 40 control subjects without cirrhosis treated at the alcohol and liver outpatient clinics and the gastroenterology ward of the Cassiano Ant?nio de Moraes University Hospital(Hospital Universitário Cassiano Ant?nio de Moraes- HUCAM), Espírito Santo, Brazil.RESULTS The average FAB score was lower for the cirrhotic than for the non-cirrhotic patients(10.6 ± 3.67 vs 12.25 ± 2.72, P = 0.015). The FAB score was lower for the cirrhotic patients with OHE than for the patients without OHE(8.25 ± 4.55 vs 11.14 ± 3.25, P = 0.027). The total FAB score was lower for the cirrhotic patients without OHE than for the non-cirrhotic patients, although this difference was not significant(11.14 ± 3.25 vs 12.25 ± 2.72, P = 0.067). Nevertheless, the difference in the scores on the subtest that assessed the ability to inhibit a response previously conditioned to a stimulus was significant(1.72 ± 0.93 vs 2.2 ± 0.85, P = 0.011).CONCLUSION The present study indicates that the FAB is a promising tool for outpatient minimal HE screening and the assessment of HE severity.     

Clinical scenarios for the use of S100β as a marker of hepatic encephalopathy

AIM: To evaluate the association between serum concentrations of S100β in patients with cirrhosis and the presence of low grade hepatic encephalopathy(HE).METHODS: This was a cross-sectional study. The population was categorized into four groups healthy subjects, cirrhosis without HE, cirrhosis with covert hepatic encephalopathy(CHE) and cirrhosis with overt HE. Kruskal-Wallis, Mann Whitney's U with Bonferroni adjustment Spearman correlations and area under the ROC were used as appropriate.RESULTS: A total of 61 subjects were included, 46 cirrhotic patients and 15 healthy volunteers. S100β values were different among all groups, and differences remained significant between groups 1 and 2(P 0.001), and also between groups 2 and 3(P = 0.016), but not between groups 3 and 4. In cirrhotic patients with HE S100β was higher than in patients without HE [0.18(0.14-0.28) ng/m L vs 0.11(0.06-0.14) ng/m L, P 0.001]. There was a close correlation between serum concentrations of S100β and psychometric hepatic encephalopathy score in patients with cirrhosis without HE compared to the patients with cirrhosis with CHE(r =-0.413, P = 0.019). ROC curve analysis yielded 0.13 ng/m L as the best cutoff value of S100β for the diagnosis of HE(sensitivity 83.3%, specificity 63.6%).CONCLUSION: Serum concentrations of S100β are higher in patients with cirrhosis than in healthy volunteers, and are further increased in the presence of hepatic encephalopathy. The results suggest that serum biomarkers such as S100β could help in the correct characterization of incipient stages of HE.     

Risk calculators—methods,development, implementation,and validation

Introduction

A surgical risk calculator (SRC) estimates the probabilities of unfavorable outcomes such as complications or death after a specific surgery. The risk estimates are based on information regarding the patient’s medical history and his current status. They are calculated using risk models derived from the analysis of data from a large number of previous patients in a similar clinical situation.

Methods

This paper discusses several aspects of the SRC development and its implementation into clinical practice: the development of the statistical risk models, their validation and software implementation, the use of the SRC output for shared decision making in clinical settings, and the evaluation of the SRC’s impact on individual patient outcomes as well as on the institution’s quality of care of the clinical institution.

Results

Probably the most elaborate SRC is the ACS NSQIP SRC. A comparable project was started by the German Society for Visceral and General Surgery (DGAV) in the framework of its Study, Documentation, and Quality Center (StuDoQ). It is relevant to consider that the transportability of a SRC from a US American to a German setting is not straightforward.

Conclusions

Risk calculators are important instruments for shared decision making between patients and doctor. Their implementation into clinical practice has to solve technical issues, and it is related to appropriate training of clinicians. There are specific study designs to evaluate the clinical impact of a SCR.

     

α-Ketoglutaramate: an overlooked metabolite of glutamine and a biomarker for hepatic encephalopathy and inborn errors of the urea cycle

Glutamine metabolism is generally regarded as proceeding via glutaminase-catalyzed hydrolysis to glutamate and ammonia, followed by conversion of glutamate to α-ketoglutarate catalyzed by glutamate dehydrogenase or by a glutamate-linked aminotransferase (transaminase). However, another pathway exists for the conversion of glutamine to α-ketoglutarate that is often overlooked, but is widely distributed in nature. This pathway, referred to as the glutaminase II pathway, consists of a glutamine transaminase coupled to ω-amidase. Transamination of glutamine results in formation of the corresponding α-keto acid, namely, α-ketoglutaramate (KGM). KGM is hydrolyzed by ω-amidase to α-ketoglutarate and ammonia. The net glutaminase II reaction is: L?‐?Glutamine?+?α?‐?keto acid?+?H₂O → α?‐?ketoglutarate?+?L?‐?amino acid?+?ammonia. In this mini-review the biochemical importance of the glutaminase II pathway is summarized, with emphasis on the key component KGM. Forty years ago it was noted that the concentration of KGM is increased in the cerebrospinal fluid (CSF) of patients with hepatic encephalopathy (HE) and that the level of KGM in the CSF correlates well with the degree of encephalopathy. In more recent work, we have shown that KGM is markedly elevated in the urine of patients with inborn errors of the urea cycle. It is suggested that KGM may be a useful biomarker for many hyperammonemic diseases including hepatic encephalopathy, inborn errors of the urea cycle, citrin deficiency and lysinuric protein intolerance.     

Shunt occlusion for portosystemic shunt syndrome related refractory hepatic encephalopathy—A single-center experience in 21 patients from Kerala

Introduction

Large spontaneous portosystemic shunts (SPSS) are seen in a subset of patients with liver disease and medically refractory recurrent/persistent hepatic encephalopathy (MRHE). Shunt occlusion has been shown to improve clinical outcomes.

Methods

We retrospectively analyzed patient characteristics, SPSS attributes, procedural features, baseline clinical and investigational parameters, neurological outcomes, adverse effects (procedure and portal hypertension related), and risk factors predicting outcomes in liver disease patients undergoing shunt occlusion procedure for MRHE.

Results

Between October 2016 and July 2017, 21 patients (Child-Pugh score, CTP 6 to 13) with mean model of end-stage liver disease (MELD) and MELD-sodium scores 15.7 and 19.3 respectively with MRHE [3-cirrhotic Parkinsonism (CP)] were diagnosed to have single or multiple large SPSSs. A total of 29 shunts were occluded (1 surgical, 20 non-surgical). Recurrent and persistent HE and CP markedly improved in the short (n=20, 1 to 3 months), intermediate (n=12, 3 to 6 months), and long (n=7, 6 to 9 months) follow up. None had spontaneous or persistent HE at a median follow up 105 (30 to 329) days (p<0.05). Motor, speech, sleep abnormalities, daily activities of living, and liver disease severity scores improved significantly on follow up. Baseline arterial ammonia showed a statistically significant reduction in all time periods of follow up after shunt occlusion (p<0.05). CTP >11 predicted mortality post shunt occlusion (p=0.04). Embolization of large SPSS in liver disease patients with MRHE and modestly preserved liver function is safe and efficacious and associated with improved quality of life and can function as a bridge to liver transplantation in accurately selected patients.

     

National project for excellence in geriatric care education—A comprehensive,innovative and practical program for undergraduate and graduate students in Taiwan

Taiwan has been experiencing a rapid increase in the aging population. A comprehensive and practical education program on geriatric care for learners of different levels is fundamental to preparing future professionals to provide quality care for the elderly. With financial aid from the Ministry of Education, Ministry of Interior and National Department of Health, Chung Shan Medical University (CSMU) was able to establish a National Project for Excellence in Geriatric Care Education (NPEGCE). The Project focuses on enhancing the academic and practical experiences of learners at both undergraduate and graduate levels in understanding and working with the elderly. The philosophy underlying the curriculum design is “LOVE”, combining the spirit of “life, obligation, vitality, and expertise”. The NPEGCE provides students with core and elective courses across disciplines pertinent to the study of gerontology and geriatrics with class structures emphasizing problem-based small group discussion. The features of the NPEGCE are: (1) to enhance students’ competence for their future careers; (2) to emphasize research ability in gerontology; (3) to launch a faculty team on geriatric education; (4) to construct a model of evaluation on geriatric care education; (5) to facilitate cross-field interaction and collaboration among academia, enterprise and governmental organizations; and (6) to promote opportunities for international academic and practical cooperation. The NPEGCE is the first comprehensive geriatric education program in Taiwan that offers competence certificates to students from different disciplines at undergraduate and graduate levels. So far, we have more than 30 faculty members and some 30 preceptors engaged in the work of teaching, practicum and research. We have successfully recruited 355 undergraduate and 45 graduate students since the inception of the NPEGCE in January 2007. For sustained development, the Center for Education and Research on Geriatrics and Gerontology, a permanent institute within CSMU, was established in January 2009 to run and promote the NPEGCE as well as its research on aging in central Taiwan.     

Methodologic research on TIMP—1,TIMP—2 detection as a new diagnostic index for hepatic fibrosis and its significance

AIM: To set up a new method to detect tissue inhibitors of metalloproteinase-1 and -2(TIMP-1 and TIMP-2) in sera of patients with hepatic cirrhosis, and to investigate the expression and location of TIMP-1 and TIMP-2 in liver tissue of patients with hepatic cirrhosis, and the correlation between TIMPs in liver and those in sera so as to discuss whether TIMPs can be used as a diagnosis index of hepatic fibrosis. METHODS: The monoclonal antibodies (McAbs) of TIMP-1 and TIMP-2 were used to sensitize erythrocytes, and solid-phase absorption to sensitized erythrocytes (SPASE) was used to detect TIMP-1 and TIMP-2 in the sera of patients with hepatic cirrhosis. Meanwhile, with the method of in situ hybridization and immunohistochemistry, we studied the mRNA expression and antigen location of TIMP-1 and TIMP-2 in the livers of 40 hepatic cirrhosis patients with pathologic diagnosis. RESULTS: With SPASE, they were 16.4% higher in the acute hepatitis group, 33.3% higher in the chronic hepatitis group, and the positive rates were 73.6% and 61.2% respectively in sera of hepatic cirrhosis patients, which were remarkably higher than those in chronic hepatitis and acute hepatitis group (P<0.001). In 40 samples of hepatic cirrhosis tissues, all of them showed positive expression of TIMP-1 and TIMP-2 mRNA detected with immunohistochemistry or in situ hybridization (positive rate was 100%). Expression of TIMPs in different degrees could be found in liver tissue with cirrhosis. TIMPs were located in cytoplasm of liver cells of patients with hepatic cirrhosis. There was a significant correlation between serum TIMPs level and liver TIMPs level. CONCLUSION: SPASE is a useful method to detect the TIMP-1 and TIMP-2 in sera of patients with hepatic cirrhosis, and TIMP-1 and TIMP-2 can be considered as a useful diagnostic index of hepatic fibrosis, especially TIMP-1.     

Percutaneous support of the failing left and right ventricle—recommendations for the use of mechanical device therapy

Patients in cardiogenic shock and acute heart failure show high mortality and morbidity despite aggressive and invasive methods such as percutaneous coronary intervention and the use of mechanical support devices. Percutaneous implantation of active hemodynamic support is often the only option for hemodynamic stabilization of patients in cardiogenic shock. Therefore, current guidelines support the use of these devices. Standardized protocols and clinical algorithms for the use of these support devices decrease mortality in these patients. The aim of this review is an overview of current therapies of cardiogenic shock with special focus on mechanical support devices and the suggestion of a clinical algorithm for the differential use of current devices as well as the hemodynamic monitoring of such patients in order to reduce mortality in cardiogenic shock.     

The WHO diagnostic criteria for polycythemia vera—role of red cell mass versus hemoglobin/hematocrit level and morphology

Regarding diagnosis of polycythemia vera (PV), discussion persists about hemoglobin (Hb) and/or hematocrit (Hct) threshold values as surrogate markers for red cell mass (RCM) and the diagnostic impact of bone marrow (BM) morphology. We performed a retrospective study on 290 patients with PV (151 males, 139 females; median age 65 years) presenting with characteristic BM features (initial biopsies, centralized evaluation) and endogenous erythroid colony (EEC) formations. This cohort included (1) a group of 229 patients when following the 2008 versus 256 patients diagnosed according to the 2016 World Health Organization (WHO) guidelines, all presented with increased RCM; (2) masked PV patients with low Hb (n?=?143)/Hct (n?=?45) recruited from the 2008 WHO cohort; (3) a cohort of 17 PV patients with elevated diagnostic Hb/Hct levels but low RCM; and (4) nine PV patients with increased RCM, opposing low Hb/Hct values. All patients were treated according to current PV guidelines (phlebotomies 87%, hydroxyurea 79%, and acetylsalicylic acid 87%). Applying the 2016 WHO criteria significantly increased concordance between RCM and Hb values compared with the 2008 WHO criteria (90 vs. 43% in males and 83 vs. 64% in females). Further analysis of the WHO 2016 PV cohort revealed that increased RCM is associated with increased Hb/Hct (93.8/94.6%). Our study supports and extends the diagnostic impact of the 2016 revised WHO classification for PV by highlighting the importance of characteristic BM findings and implies that Hb/Hct threshold values may be used as surrogate markers for RCM measurements.     

Post-usual meal C-peptide as a reliable and practical alternative to C-peptide following glucagon or standardized mixed-meal for β-cell reserve: a comparative study between three stimulatory methods in different types of diabetes

International Journal of Diabetes in Developing Countries - Formal stimulation tests for β-cell secretory reserve, like glucagon stimulation test (GST) or mixed meal tolerance test, are...     

Is 2D speckle tracking echocardiography useful for detecting and monitoring myocardial dysfunction in adult m.3243A&gt;G carriers? — a retrospective pilot study

Objectives

Cardiomyopathy is a common complication of mitochondrial disorders, associated with increased mortality. Two dimensional speckle tracking echocardiography (2DSTE) can be used to quantify myocardial deformation. Here, we aimed to determine the usefulness of 2DSTE in detecting and monitoring subtle changes in myocardial dysfunction in carriers of the 3243A>G mutation in mitochondrial DNA.

Methods

In this retrospective pilot study, 30 symptomatic and asymptomatic carriers of the mitochondrial 3243A>G mutation of whom two subsequent echocardiograms were available were included. We measured longitudinal, circumferential and radial strain using 2DSTE. Results were compared to published reference values.

Results

Speckle tracking was feasible in 90 % of the patients for longitudinal strain. Circumferential and radial strain showed low face validity (low number of images with sufficient quality; suboptimal tracking) and were therefore rejected for further analysis. Global longitudinal strain showed good face validity, and was abnormal in 56–70 % (depending on reference values used) of the carriers (n?=?27). Reproducibility was good (mean difference of 0.83 for inter- and 0.40 for intra-rater reproducibility; ICC 0.78 and 0.89, respectively). The difference between the first and the second measurement exceeded the measurement variance in 39 % of the cases (n?=?23; feasibility of follow-up 77 %).

Discussion

Even in data collected as part of clinical care, two-dimensional strain echocardiography seems a feasible method to detect and monitor subtle changes in longitudinal myocardial deformation in adult carriers of the mitochondrial 3243A>G mutation. Based on our data and the reported accuracy of global longitudinal strain in other studies, we suggest the use of global longitudinal strain in a prospective follow-up or intervention study.