Early diagnosis of anastomotic leakage after colorectal surgery by the Dutch leakage score, serum procalcitonin and serum C-reactive protein: study protocol of a prospective multicentre observational study by the Italian ColoRectal Anastomotic Leakage (iC.

BACKGROUND: Anastomotic leakage (AL) is a dreaded major complication after colorectal surgery. There is no uniform definition of anastomotic dehiscence and leak. Over the years many risk factors have been identified (distance of anastomosis from anal verge, gender, BMI, ASA score) but none of these allows an early diagnosis of AL. The DUtch LeaKage (DULK) score, C reactive protein (CRP) and procalcitonin (PCT) have been identified as early predictors for anastomotic leakage starting from postoperative day (POD) 2-3. The study was designed to prospectively evaluate AL rates after colorectal resections, in order to give a definite answer to the need for clear risk factors, and testing the diagnostic yeld of DULK score and of laboratory markers. Methods and analysis. A prospective enrollment for all patients undergoing elective colorectal surgery with anastomosis carried out from September 2017 to September 2018 in 19 Italian surgical centers. OUTCOME MEASURES: preoperative risk factors of anastomotic leakage; operative parameters; leukocyte count, serum CRP, serum PCT and DULK score assessment on POD 2 and 3. Primary endpoint is AL; secondary endpoints are minor and major complications according to Clavien-Dindo classification; morbidity and mortality rates; readmission and reoperation rates, length of postoperative hospital stay (Retrospectively registered at ClinicalTrials.gov Identifier: NCT03560180, on June 18, 2018). Ethics. The ethics committee of the "Comitato Etico Regionale delle Marche - C.E.R.M." reviewed and approved this study protocol on September 7, 2017 (protocol no. 2017-0244-AS). All the participating centers submitted the protocol and obtained authorization from the local Institutional Review Board.

Recent developments in the diagnosis and treatment of covert/minimal hepatic encephalopathy.

The terms minimal hepatic encephalopathy and covert hepatic encephalopathy are defined. Clinical assessment is unreliable and both require the use of diagnostic tools. Of these, psychometric tests are the most widely used. They require proper standardization and may be biased by patient cooperation or lack thereof. The measure of the critical flicker frequency and of the electroencephalogram, possibly quantified, are also useful. The alteration of any of them is not strictly parallel in size and may vary from patient to patient. When possible, the use of multiple measures might increase diagnostic reliability. These functional measures should be interpreted within the clinical/biochemical profile of the patient to exclude other disorders. A flow chart for treatment is proposed on the basis of current knowledge.

The self-morningness/eveningness (Self-ME): An extremely concise and totally subjective assessment of diurnal preference.

The assessment of diurnal preference, or the preferred timing of sleep and activity, is generally based on comprehensive questionnaires such as the Horne-Östberg (HÖ). The aim of the present study was to assess the reliability of a subject's self-classification as extremely morning (Self-MM), more morning than evening (Self-M), more evening than morning (Self-E) or extremely evening (Self-EE) type, based on the last question of the HÖ (Self-ME). A convenience sample of 461 subjects [23.8 ± 4.7 years; 322 females] completed a full sleep-wake assessment, including diurnal preference (HÖ), night sleep quality (Pittsburgh Sleep Quality Index, PSQI), daytime sleepiness (Karolinska Sleepiness Scale, KSS), and habitual sleep-wake timing (12 d sleep diaries; n = 296). Significant differences in HÖ total score were observed between Self-ME classes, with each class being significantly different from neighboring classes (p < 0.0001). Significant differences in sleep-wake timing (bed time, try to sleep and sleep onset, wake up, and get up time) were observed between Self-ME classes. Such differences were maintained when sleep-wake habits were analysed separately on work and free days, and also in a smaller group of 67 subjects who completed the Self-ME as a stand-alone rather than as part of the original questionnaire. Significant differences were observed in the time-course of subjective sleepiness by Self-ME class in both the large and the small group, with Self-MM and Self-M subjects being significantly more alert in the morning and sleepier in the evening hours compared with their Self-E and Self-EE counterparts. Finally, significant differences were observed in night sleep quality between Self-ME classes, with Self-EE/Self-E subjects sleeping worse than their Self-MM/Self-M counterparts, and averaging just over the abnormality PSQI threshold of 5. In conclusion, young, healthy adults can define their diurnal preference based on a single question (Self-ME) in a way that reflects their sleep-wake timing, their sleepiness levels over the daytime hours, and their night sleep quality. Validation of the Self-ME across the decades and in diseased populations seems worthy.

Sleep and circadian rhythms in hospitalized patients with decompensated cirrhosis: effect of light therapy.

Patients with liver cirrhosis often exhibit sleep-wake abnormalities, which are, at least to some extent, circadian in origin. A relatively novel non-pharmacological approach to circadian disruption is appropriately timed bright light therapy. The aims of this pilot study were to investigate sleep-wake characteristics of a well-characterized population of inpatients with cirrhosis, and to evaluate the efficacy of bright light therapy in the hospital setting. Twelve consecutive inpatients with cirrhosis underwent complete sleep-wake assessment, to include qualitative and semi-quantitative (actigraphic) indices of night-time sleep quality, daytime sleepiness, diurnal preference, habitual sleep timing, quality of life, mood and circadian rhythmicity [i.e. urine collections for measurement of the melatonin metabolite 6-sulphatoxymelatonin (aMT6s)]. Patients showed extremely impaired night sleep quality (Pittsburg Sleep Quality Index global score: 16.3 ± 2.1) and daytime sleepiness was common (Epworth Sleepiness Scale: 8.3 ± 3.2). Five patients were randomly assigned to a single room in which lighting was controlled in relation to timing, spectral composition and intensity (lights on at 06:30 and off at 22:30, blue-enriched, more intense light in the morning, red-enriched, less intense light in the afternoon/evening); the others stayed in identical rooms with standard lighting. Sleep diaries revealed poor sleep quality, prolonged sleep latency (67 ± 138 min) and a reduced sleep efficiency (69 ± 21%). These features were confirmed by actigraphy (sleep efficiency: 71 ± 13%; fragmentation index: 55 ± 15%). Quality of life was globally impaired, and mood moderately depressed (Beck Depression Inventory: 19.4 ± 7.9). Seven patients underwent serial urine collections: no circadian aMT6s rhythm was detected in any of them, neither at baseline, nor during the course of hospitalization in either room (n = 4). In conclusion, sleep and circadian rhythms in hospitalized, decompensated patients with cirrhosis are extremely compromised. Treatment with bright light therapy did not show obvious, beneficial effects, most likely in relation to the severity of disturbance at baseline.

Acute hyperammonaemia induces a sustained decrease in vigilance, which is modulated by caffeine.

UNLABELLED: Hyperammonaemia is observed after prolonged, intense exercise, or in patients with hepatic failure. In the latter, it is associated with a set of neurological and psychiatric abnormalities termed hepatic encephalopathy. THE AIMS OF OUR STUDY WERE: 1. to measure vigilance in a condition of induced hyperammonaemia; 2. to assess whether caffeine modulates the effects of hyperammonaemia on vigilance, if any. Ten healthy volunteers (28.5 ± 5 years; 5 males) underwent three experimental sessions consisting of two-hourly measurements of capillary ammonia, subjective sleepiness (Karolinska Sleepiness Scale) and vigilance (Psychomotor Vigilance Task, PVT), in relation to the intake of breakfast (+/-coffee), an amino acid mixture which induces hyperammonaemia (amino acid challenge; AAC), and AAC+coffee (only for participants who had coffee with their standard breakfast). The AAC resulted in: 1. the expected increase in capillary ammonia levels, with highest values at approximately 4 h after the administration; 2. a significant increase in subjective sleepiness ratings; 3. a sustained increase in PVT-based reaction times. When caffeine was administered after the AAC, both subjective sleepiness and the slowing in RTs were significantly milder than in the AAC-only condition. In conclusion, acute hyperammonaemia induces an increase in subjective sleepiness and a sustained decrease in vigilance, which are attenuated by the administration of a single espresso coffee.

Insight into the relationship between brain/behavioral speed and variability in patients with minimal hepatic encephalopathy.

OBJECTIVE: Intra-individual variability (IIV) of response reaction times (RTs) and psychomotor slowing were proposed as markers of brain dysfunction in patients with minimal hepatic encephalopathy (MHE), a subclinical disorder of the central nervous system frequently detectable in patients with liver cirrhosis. However, behavioral measures alone do not enable investigations into the neural correlates of these phenomena. The aim of this study was to investigate the electrophysiological correlates of psychomotor slowing and increased IIV of RTs in patients with MHE. METHODS: Event-related potentials (ERPs), evoked by a stimulus-response (S-R) conflict task, were recorded from a sample of patients with liver cirrhosis, with and without MHE, and a group of healthy controls. A recently presented Bayesian approach was used to estimate single-trial P300 parameters. RESULTS: Patients with MHE, with both psychomotor slowing and higher IIV of RTs, showed higher P300 latency jittering and lower single-trial P300 amplitude compared to healthy controls. In healthy controls, distribution analysis revealed that single-trial P300 latency increased and amplitude decreased as RTs became longer; however, in patients with MHE the linkage between P300 and RTs was weaker or even absent. CONCLUSIONS: These findings suggest that in patients with MHE, the loss of the relationship between P300 parameters and RTs is related to both higher IIV of RTs and psychomotor slowing. SIGNIFICANCE: This study highlights the utility of investigating the relationship between single-trial ERPs parameters along with RT distributions to explore brain functioning in normal or pathological conditions.

Ammonia-related changes in cerebral electrogenesis in healthy subjects and patients with cirrhosis.

OBJECTIVE: To study the effect of hyperammonaemia on the wake electroencephalogram (EEG) of patients with cirrhosis and healthy volunteers. METHODS: Wake EEGs were recorded prior to and after the induction of controlled hyperammonaemia in 10 patients with cirrhosis and 10 matched healthy volunteers. RESULTS: At baseline, patients had higher ammonaemia than healthy volunteers and their dominant EEG rhythm was slower and of higher amplitude. Induced hyperammonaemia resulted in increased spectral power over most of the scalp in healthy volunteers and decreased frequency along the anterior-posterior midline in patients. CONCLUSIONS: These findings suggest different effects of hyperammonaemia on the wake EEG in relation to baseline/peak ammonia levels. SIGNIFICANCE: The wake EEG is sensitive to hyperammonaemia and power-based EEG parameters may help in its neurophysiological definition, which, to date, has generally been based on EEG frequency indices.

A patients' and caregivers' perspective on hepatic encephalopathy.

Awareness of previous hepatic encephalopathy (HE) and compliance with treatment can probably reduce HE recurrence. The aim of this study was to assess the degree of awareness of previous HE and its treatment in a group of cirrhotic patients and their caregivers. Thirty-five cirrhotic patients with a history of HE and their caregivers (n = 31) were enrolled. Patients underwent evaluation of HE (clinical, psychometry and electroencephalography), quality of life (SF36 questionnaire), and awareness of HE/treatment on an ad hoc questionnaire (QAE). Caregivers underwent the QAE plus the Caregiver Burden Inventory. On the day of study, 7 patients were unimpaired, 8 had minimal and 20 low-grade overt HE. Of the patients, 37 % were aware of previous HE, 6 % of being on treatment and 6 % understood treatment effects. Of the caregivers, 48 % were aware of previous HE, 6 % of their relative being on treatment and 6 % understood treatment effects. Significant correlations were observed between neuropsychiatric status/linear HE indices and both the patients' quality of life and the caregivers' burden. In conclusion, HE awareness was poor in both patients and caregivers, most likely in relation to insufficient/inadequate provision of information.

Neuropsychological tools in hepatology: a survival guide for the clinician.

Neuropsychological assessment has three main applications in clinical hepatology: (i) to detect, grade and monitor liver failure-related cognitive alterations in end-stage liver disease (hepatic encephalopathy), (ii) to substantiate complaints of attention or concentration difficulties in patients with non-cirrhotic chronic hepatitis C viral infection, and (iii) to screen patients who are being considered for liver transplantation for early signs of dementia. However, there is limited agreement on how cognitive assessment should be conducted in these patients, and how results should be interpreted and used to implement clinical decisions. In this review, we summarize the available literature on neuropsychological dysfunction in patients with cirrhosis and with chronic hepatitis C viral infection and provide some guidance on how to utilize neuropsychological assessment in practice.

Does the nasogastric tube has a role in elective colo-rectal surgery?

INTRODUCTION: Routine use of nasogastric tubes (NGT) after abdominal operations is intended to hasten the return of bowel function, diminish the risk of anastomotic leakage and prevent pulmonary complications. The aim of our study was to prospectively assess the tolerability and the safety of the non use of NGT after elective colorectal open operations. PATIENTS AND METHODS: Between March 2009 and December 2010, 110 consecutive patients underwent colo-rectal elective open surgery for neoplasm without nasogastric decompression. We analyzed the incidence of nausea and vomiting, the pulmonary complications, the return of bowel function the deep wound breakdown (fascial dehiscence) and the anastomotic leakage. RESULTS: Only 15 patients (13,6%) reported nausea without vomiting immediately after surgery and 9 cases of vomiting were observed (8%), requiring the insertion of the NGT (nasogastric tube) in 5 (4,5%). A total of 105 patients (96,3%) were NGT free. No deep wound dehiscence was observed and only one real pneumonia occurred. Anastomotic dehiscence occurred in 4 patients (3,6%) and a second surgical procedure was needed in three cases. The return of bowel function, except in the last four patients, occurred in 3,8 days average (range 2-7 days). CONCLUSION: We confirm the uselessness of the NGT in the framework of fast track program adopted in elective open colo-rectal surgery.

A novel method for the determination of the EEG individual alpha frequency.

The individual alpha frequency (IAF) is one of the most common tools used to study the variability of EEG rhythms among subjects. Several approaches have been proposed in the literature for IAF determination, including the popular peak frequency (PF) method, the extended band (EB) method, and the transition frequency (TF) method. However, literature techniques for IAF determination are over-reliant on the presence of peaks in the EEG spectrum and are based on qualitative criteria that require visual inspection of every individual EEG spectrum, a task that can be time consuming and difficult to reproduce. In this paper a novel channel reactivity based (CRB) method is proposed for IAF computation. The CRB method is based on quantitative indexes and criteria and relies on task-specific alpha reactivity patterns rather than on the presence of peaks in the EEG spectrum. Application of the technique to EEG signals recorded from 19 subjects during a cognitive task demonstrates the effectiveness of the CRB method and its capability to overcome the limits of PF, EB, and TF approaches.

Review article: the design of clinical trials in hepatic encephalopathy--an International Society for Hepatic Encephalopathy and Nitrogen Metabolism (ISHEN) consensus statement.

BACKGROUND: The clinical classification of hepatic encephalopathy is largely subjective, which has led to difficulties in designing trials in this field. AIMS: To review the current classification of hepatic encephalopathy and to develop consensus guidelines on the design and conduct of future clinical trials. METHODS: A round table was convened at the 14th International Society for Hepatic Encephalopathy and Nitrogen Metabolism (ISHEN) meeting. Key discussion points were the nomenclature of hepatic encephalopathy and the selection of patients, standards of care and end-points for assessing the treatment and secondary prevention of hepatic encephalopathy. RESULTS: It was generally agreed that severity assessment of hepatic encephalopathy in patients with cirrhosis, whether made clinically or more objectively, should be continuous rather than categorical, and a system for assessing the SONIC (Spectrum of Neuro-cognitive Impairment in Cirrhosis) was proposed. Within this system, patients currently classified as having minimal hepatic encephalopathy and Grade I hepatic encephalopathy would be classified as having Covert hepatic encephalopathy, whereas those with apparent clinical abnormalities would continue to be classified as overt hepatic encephalopathy. Some aspects of the terminology require further debate. Consensus was also reached on the patient populations, standards of care and endpoints to assess clinical trial outcomes. However, some compromises had to be made as there is considerable inter- and intravariability in the availability of some of the more objective surrogate performance markers. CONCLUSIONS: The objectives of the round table were met. Robust, defendable guidelines for the conduct of future studies into hepatic encephalopathy have been provided. Outstanding issues are few and will continue to be discussed.

Blood pressure control has distinct effects on executive function, attention, memory and markers of cerebrovascular damage.

Hypertension causes cognitive impairment, involving mainly executive functions, but the effect of blood pressure (BP) control on the different cognitive domains is still debated. We correlated executive function, attention and memory with BP control and cerebrovascular damage in 60 undemented middle-aged hypertensives at baseline and after 6-year follow-up. At first evaluation, the patients with poor BP control had higher score of white matter lesions, reduced cerebrovascular reserve capacity and greater carotid intima-media thickness (IMT) than those with good BP control. Performance on executive tests correlated with IMT and with performance on attention tests, which was impaired by low diastolic BP. At long-term follow-up, performance in attention and executive tests improved in spite of the minor improvement of BP control, increased IMT and worse memory. Low diastolic BP has a negative effect on attention, which affects executive performance at first cross-sectional examination. This confounding effect has to be taken into consideration when planning studies on cognitive function. Longitudinal studies are required to unravel the effect of BP control on cognitive function, as only long-term antihypertensive treatment improves both attention and executive performance.

Neurocognitive-neurological complications of liver transplantation: a review.

Neurological complications are common after liver transplantation (LT) and they are associated with a significant morbidity. Long-term effects of LT on cognitive and psychological outcomes are not clear. The objective of this study was to summarize the present knowledge on the neurological and cognitive complications of LT, resulting from a systematic review of the literature in the last 10 years. Several studies have investigated the incidence and the pathophysiology of neurological complications; in contrast, the knowledge of cognitive and psychological status after LT is poor. Currently, the effect of LT on mental performance is debated. Some studies have shown an improvement of cognitive function after OLTX and, at the same time, a persistence of different cognitive deficits. In addition, the quality of life (QoL) and the psychological status after LT seem to improve but LT recipients have significant deficiencies in most QoL domains. Consequently, future studies are necessary in order to investigate cognitive alterations and QoL in LT recipients.

Consensus on the use of neurophysiological tests in the intensive care unit (ICU): electroencephalogram (EEG), evoked potentials (EP), and electroneuromyography (ENMG).

STUDY AIM: To provide a consensus of European leading authorities about the optimal use of clinical neurophysiological (CN) tests (electroencephalogram [EEG]; evoked potentials [EP]; electroneuromyography [ENMG]) in the intensive care unit (ICU) and, particularly, about the way to make these tests clinically useful for the management of individual patients. METHODS: This study gathered together several European clinical neurophysiologists and neurointensivists whose leading contributions in the adult or paediatric ICU and in continuous neuromonitoring had been peer-acknowledged. It was based on both a literature review and each participant's own experience. Given the methodological impossibility to gather studies fulfilling criteria of evidence-based medicine, this article essentially relies on expert opinions that were gained after several rounds, in which each expert was invited to communicate his own contribution to all other experts. A complete consensus has been reached when submitting the manuscript. RESULTS: What the group considered as the best classification systems for EEG and EP abnormalities in the ICU is first presented. CN tests are useful for diagnosis (epilepsy, brain death, and neuromuscular disorders), prognosis (anoxic ischemic encephalopathy, head trauma, and neurologic disturbances of metabolic and toxic origin), and follow-up, in the adult, paediatric, and neonatal ICU. Regarding prognosis, a clear distinction is made between these tests whose abnormalities are indicative of an ominous prognosis and those whose relative normalcy is indicative of a good prognosis. The prognostic significance of any test may vary as a function of coma etiology. CONCLUSION: CN provides quantitative functional assessment of the nervous system. It can be used in sedated or curarized patients. Therefore, it should play a major role in the individual assessment of ICU patients.

Electroencephalographic analysis for the assessment of hepatic encephalopathy: comparison of non-parametric and parametric spectral estimation techniques.

OBJECTIVE: To compare electroencephalographic spectral analysis obtained by periodogram (calculated by means of Fast Fourier Transform) and autoregressive (AR) modelling for the assessment of hepatic encephalopathy. METHODS: The mean dominant frequency (MDF) and the relative power of delta, theta, alpha, and beta bands were computed by both techniques from the electroencephalograms (EEG) of 201 cirrhotics and were evaluated in the clinical and prognostic assessment of the patients. RESULTS: The values of all the five indexes computed by periodogram and AR modelling matched each other, but the latter provided stable values after the analysis of fewer epochs. Independently of the technique, the relative power of theta and alpha bands fitted the clinical data and had prognostic value. The relative power of beta and delta bands computed by AR modelling fitted more closely with clinical data fitted the clinical data more closely. CONCLUSIONS: The electroencephalographic spectral indexes obtained by periodogram and AR modelling were found to be, on average, undistinguishable, but the latter appeared less sensitive to noise and provided a more reliable assessment of low-power bands.

Subjective satisfaction and quality of life in patients prior to listing for liver transplantation.

OBJECTIVES: Differences in health-related quality of life (HR-QoL) perception between alcohol abusing and non-substance-dependent subjects with liver cirrhosis could depend on differences in personality profile and influence management of patients awaiting liver transplant. METHODS: We compared the perceptions of disease state in 78 male patients of similar disease severity divided into 2 groups based on etiology of cirrhosis: 47% had alcoholic cirrhosis, and 53% had hepatitis C virus(HCV)-related cirrhosis without alcohol abuse. Patients' perception of disease state was determined using the SAT-P questionnaire (a self-administered questionnaire that provides a global assessment of perceived HR-QoL and subjective well-being). The assessment yields 2 scales: an analytic scale based on 32 variables and a synthetic scale based on 5 factors. RESULTS: In patients with alcohol-related disease, ''psychological function'' was found to be more impaired,while ''sleep, diet, and free time'' was less impaired compared with subjects with HCV-related cirrhosis, suggesting dysfunction related to substance abuse with personality disturbance. CONCLUSIONS: The perception of disease state is different in alcohol-abusing patients with cirrhosis compared with those with cirrhosis unrelated to alcohol.

Neurological complications after orthotopic liver transplantation.

BACKGROUND: The number of orthotopic liver transplantation performed each year is increasing due to increased safety and logistic facilities. Therefore, the importance of reducing adverse events is progressively growing. AIM: To review present knowledge on the neurological complications of orthotopic liver transplantation. METHODS: The epidemiology, the clinical features and the pathophysiology of the neurological complications of orthotopic liver transplants, resulting from a systematic review of the literature in the last 25 years, are summarized. RESULTS AND CONCLUSIONS: The review highlights that a relevant variety of neurological adverse events can occur in patients undergoing orthotopic liver transplantation. The knowledge of neurological complications of orthotopic liver transplantation is important for transplantation teams to reduce their prevalence and improve their management. In addition, the likelihood of neurological adverse effects provides evidence for the need of a careful cognitive and neurological work up of patients in the orthotopic liver transplantation waiting list, in order to recognize and interpret neurological dysfunction occurring after orthotopic liver transplantation.

The EEG assessment of low-grade hepatic encephalopathy: comparison of an artificial neural network-expert system (ANNES) based evaluation with visual EEG readings and EEG spectral analysis.

OBJECTIVE: The EEG provides an objective staging of hepatic encephalopathy (HE), but its interpretation may be biased by inter-observer variability. This study aims at comparing an entirely automatic EEG classification of HE based on an artificial neural network-expert system procedure (ANNES) with visual and spectral analysis based EEG classifications. METHODS: Two hundred and thirty-eight consecutive cirrhotic patients underwent closed-eye EEG. They were followed up for up to one-year to detect bouts of overt HE and death. The EEG was classified by ANNES, qualitative visual reading, main basic rhythm frequency and spectral analysis. The classifications were assessed on the basis of: (i) match with liver function, (ii) prognostic value and (iii) repeatability. RESULTS: All classifications were found to be related to the severity of liver failure, with cognitive findings and a history of previous bouts of HE. All of them had prognostic value on the occurrence of overt HE and on survival. The ANNES based classification was more repeatable than the qualitative visual one, and had the advantage of detecting low power EEG, but its efficiency in analyzing low-grade alterations was questionable. CONCLUSIONS: An entirely automatic - ANNES based - EEG classification of HE can improve the repeatability of EEG assessment, but further improvement of the device is required to classify mild alterations. SIGNIFICANCE: The ANNES based EEG grading of HE needs further improvements to be recommended in clinical practice, but it is already sufficient for detecting normal and clearly altered EEG tracings.