Minimal hepatic encephalopathy (mHE) has significant impact upon a liver patient's daily living and health related quality of life. Therefore a majority of clinicians agree that mHE should be ...diagnosed and treated. The optimal means for diagnosing mHE, however, is controversial. This paper describes the currently most frequently used methods—EEG, critical flicker frequency, Continuous Reaction time Test, Inhibitory Control Test, computerized test batteries such as the Cognitive Drug Research test battery, the psychometric hepatic encephalopathy score (PHES) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)—and their pros and cons.
In general, hepatic encephalopathy (HE) is defined as a brain dysfunction caused by liver insufficiency and/or portal-systemic blood shunting. This article relates to the so-called type C HE: that ...is, HE in patients with liver cirrhosis. It manifests as a wide spectrum of neurological or psychiatric abnormalities, ranging from subclinical alterations, detectable only by neuropsychological or neurophysiological assessment, to coma. Several scales have been developed for grading the extent of HE. The most often used is the West Haven criteria (WHC), which differentiate between four grades of clinically overt HE. Patients with liver cirrhosis without clinically overt symptoms of HE but neuropsychological or neurophysiological findings indicating brain dysfunction are considered to have minimal hepatic encephalopathy (MHE). For simplification, some experts suggest differentiating between covert HE (MHE plus grade I HE according to WHC) and overt HE (WHC grades II–IV). Diagnosis of both MHE and overt HE is hampered by the fact that none of the symptoms of HE or the findings in the various diagnostic measures applied are specific. Thus, a diagnosis of HE or MHE can only be made after exclusion of other possible causes of brain dysfunction.
Minimal hepatic encephalopathy (mHE) is diagnosed in patients with severe liver disease but no clinical symptoms of encephalopathy if either neuropsychological or neurophysiological tests indicate ...cerebral dysfunction and other possible causes of brain dysfunction have been excluded. mHE is characterized by deficits in attention, visuospatial orientation, visuoconstructive abilities and motor function. Accordingly, mHE can be expected to interfere with a subject's working ability, especially in those occupations that require handiwork, and driving ability. Indeed, about 60% of blue-collar workers with mHE have been shown to be assessed as unfit for work compared to only 20% of white-collar workers, and about 50% of patients with mHE have been judged unfit to drive a car in several studies. mHE interferes with a patient's quality of life and is associated with an increased risk of developing overt HE as well as increased mortality. Whether mHE is of importance for cognitive function after liver transplantation has still to be clarified.
Objectives
Intravenous application of contrast media is part of a wide spectrum of diagnostic procedures for better imaging quality. Clinical avoidance of contrast-enhanced imaging is an ever-present ...quandary in patients with impaired kidney function. The objective of this study was to estimate the risk for acute kidney injury (AKI), dialysis and mortality among patients undergoing contrast-enhanced CT compared to propensity score–matched controls (i.e. contrast-unenhanced CT). Selected cohort studies featured high-risk patients with advanced kidney disease and critical illness.
Methods
This review was designed to conform to the Preferred Reporting Items in Systematic Reviews and Meta-Analysis (PRISMA) guidelines. PubMed was searched from August 2021 to November 2021 for all-language articles without date restriction. A random-effects model (DerSimonian and Laird method) was used for meta-analysis.
Results
Twenty-one articles were included, comprising data of 169,455 patients. The overall risk of AKI was similar in the contrast-enhanced and unenhanced groups (OR: 0.97 95% CI: 0.85; 1.11,
p
= 0.64), regardless of baseline renal function and underlying disease. Substantial heterogeneity was detected (
I
2
= 90%,
p
≤ 0.0001). Multivariable logistic regression identified hypertension (
p
= 0.03) and estimated glomerular filtration rate (eGFR) ≤ 30 mL/min/1.73 m
2
(
p
= 0.0001) as factors associated with greater risk of post-contrast AKI.
Conclusions
Based on propensity score–matched pairs obtained from 21 cohort studies, we found no evidence for increased risk for AKI, dialysis or mortality after contrast-enhanced CT among patients with eGFR ≥ 45 mL/min/1.73 m
2
. In congruence with the emerging evidence in the literature, caution should be exercised in patients with hypertension and eGFR ≤ 30 mL/min/1.73 m
2
.
Key Points
•
The application of contrast media for medical imaging is not associated with higher odds for AKI, induction of renal replacement therapy, or mortality. Many comorbidities traditionally associated with greater risk for acute kidney injury do not appear to predispose for renal decline after contrast media exposure.
•
Underlying hypertension and eGFR less than or equal to 30 mL/min/1.73 m
2
seem to predispose for post-contrast acute kidney injury.
•
Propensity score matching cannot account for unmeasured influences on AKI incidence, which needs to be addressed in the interpretation of results.
The EASL Clinical Practice Guidelines (CPGs) on the management of hepatic encephalopathy (HE) present evidence-based answers to a set of relevant questions (where possible, formulated in PICO ...patient/population, intervention, comparison and outcomes format) on the definition, diagnosis, differential diagnosis and treatment of HE. The document does not cover the pathophysiology of HE and does not cover all available treatment options. The methods through which it was developed and any information relevant to its interpretation are also provided.
Objective
We previously reported an unexpectedly high seroprevalence (∼10%) of N‐methyl‐D‐aspartate‐receptor subunit‐NR1 (NMDAR1) autoantibodies (AB) in healthy and neuropsychiatrically ill subjects ...(N = 2,817). This finding challenges an unambiguous causal relationship of serum AB with brain disease. To test whether similar results would be obtained for other brain antigen‐directed AB previously connected with pathological conditions, we systematically screened serum samples of 4,236 individuals.
Methods
Serum samples of healthy (n = 1,703) versus neuropsychiatrically ill subjects (schizophrenia, affective disorders, stroke, Parkinson disease, amyotrophic lateral sclerosis, personality disorder; total n = 2,533) were tested. For analysis based on indirect immunofluorescence, we used biochip mosaics of frozen brain sections (rat, monkey) and transfected HEK293 cells expressing respective recombinant target antigens.
Results
Seroprevalence of all screened AB was comparable in healthy and ill individuals. None of them, however, reached the abundance of NMDAR1 AB (again ∼10%; immunoglobulin Ig G ∼1%). Appreciable frequency was noted for AB against amphiphysin (2.0%), ARHGAP26 (1.3%), CASPR2 (0.9%), MOG (0.8%), GAD65 (0.5%), Ma2 (0.5%), Yo (0.4%), and Ma1 (0.4%), with titers and Ig class distribution similar among groups. All other AB were found in ≤0.1% of individuals (anti–AMPAR‐1/2, AQP4, CV2, Tr/DNER, DPPX‐IF1, GABAR‐B1/B2, GAD67, GLRA1b, GRM1, GRM5, Hu, LGl1, recoverin, Ri, ZIC4). The predominant Ig class depended on antigen location, with intracellular epitopes predisposing to IgG (chi‐square = 218.91, p = 2.8 × 10−48).
Interpretation
To conclude, the brain antigen‐directed AB tested here are comparably detectable in healthy subjects and the disease groups studied here, thus questioning an upfront pathological role of these serum AB. Ann Neurol 2014;76:82–94
In light of the present therapeutic situation in COVID-19, any measure to improve course and outcome of seriously affected individuals is of utmost importance. We recap here evidence that supports ...the use of human recombinant erythropoietin (EPO) for ameliorating course and outcome of seriously ill COVID-19 patients. This brief expert review grounds on available subject-relevant literature searched until May 14, 2020, including Medline, Google Scholar, and preprint servers. We delineate in brief sections, each introduced by a summary of respective COVID-19 references, how EPO may target a number of the gravest sequelae of these patients. EPO is expected to: (1) improve respiration at several levels including lung, brainstem, spinal cord and respiratory muscles; (2) counteract overshooting inflammation caused by cytokine storm/ inflammasome; (3) act neuroprotective and neuroregenerative in brain and peripheral nervous system. Based on this accumulating experimental and clinical evidence, we finally provide the research design for a double-blind placebo-controlled randomized clinical trial including severely affected patients, which is planned to start shortly.
Numerous preclinical findings and a clinical pilot study suggest that recombinant human erythropoietin (EPO) provides neuroprotection that may be beneficial for the treatment of patients with ...ischemic stroke. Although EPO has been considered to be a safe and well-tolerated drug over 2 decades, recent studies have identified increased thromboembolic complications and/or mortality risks on EPO administration to patients with cancer or chronic kidney disease. Accordingly, the double-blind, placebo-controlled, randomized German Multicenter EPO Stroke Trial (Phase II/III; ClinicalTrials.gov Identifier: NCT00604630) was designed to evaluate efficacy and safety of EPO in stroke.
This clinical trial enrolled 522 patients with acute ischemic stroke in the middle cerebral artery territory (intent-to-treat population) with 460 patients treated as planned (per-protocol population). Within 6 hours of symptom onset, at 24 and 48 hours, EPO was infused intravenously (40,000 IU each). Systemic thrombolysis with recombinant tissue plasminogen activator was allowed and stratified for.
Unexpectedly, a very high number of patients received recombinant tissue plasminogen activator (63.4%). On analysis of total intent-to-treat and per-protocol populations, neither primary outcome Barthel Index on Day 90 (P=0.45) nor any of the other outcome parameters showed favorable effects of EPO. There was an overall death rate of 16.4% (n=42 of 256) in the EPO and 9.0% (n=24 of 266) in the placebo group (OR, 1.98; 95% CI, 1.16 to 3.38; P=0.01) without any particular mechanism of death unexpected after stroke.
Based on analysis of total intent-to-treat and per-protocol populations only, this is a negative trial that also raises safety concerns, particularly in patients receiving systemic thrombolysis.
PDF
