Presence of multiple bacterial markers in clinical samples might be useful for presumptive diagnosis of infection in cirrhotic patients with culture-negative reports.

Bacterial infections in cirrhotic patients with ascites are associated with a severe prognosis and an increased risk of death. The microbiological standard tests for the diagnosis of suspected infection, based on culture test of blood and ascitic fluid, are, in many cases (30-40 %), negative, even when patients show symptoms of infection. A multiple culture-independent protocol was applied and evaluated as a diagnostic and prognostic tool for the detection of bacterial infection in cirrhotic patients. Sixty-four culture-negative samples obtained from 34 cirrhotic patients, with PMN < 250 cells/µl of ascitic fluid, were screened for the presence of bacterial DNA, endotoxin, peptidoglycan/ß-glucan and microscopically visible bacterial cells. Correlations between the presence of multiple markers and various clinical and laboratory parameters were evaluated. Bacterial DNA was detected in 23 samples collected from 16 patients; a large part of these samples also showed the presence of other bacterial markers, which was associated with a worsening of liver functionality, a higher incidence of infections during the follow-up and a higher mortality rate in our cohort of cirrhotic patients. We believe that the detection of additional bacterial markers in bacterial DNA-positive clinical samples makes the bacterial presence and its clinical significance more realistic and might be useful as early markers of an ongoing bacterial infection and in establishing a clinical prognosis.

The effects of alcohol on gastrointestinal tract, liver and pancreas: evidence-based suggestions for clinical management.

Alcohol has a direct impact on the digestive system due to its contact with mucosal lining and interference with digestive functions. Various diseases of the gastrointestinal tract, including tumors, may be related to an excess of alcohol intake and the relationship between alcohol abuse and hepatic and pancreatic damage is well established. According to WHO, alcohol and alcohol-related diseases represent a major health problem and will probably continue to do so in the foreseeable future. In this review, we summarize the present knowledge on clinically relevant alcohol-related problems in order to provide practicing physicians with evidence-based general suggestions which might help in the management of alcohol-related gastrointestinal disorders. A thorough clinical history together with a number of questionnaires are essential for detecting alcohol dependence or abuse. Biochemical tests (nonspecific and specific) have been considered to be less sensitive than questionnaires in screening for alcohol abuse, but they may be useful in identifying relapses. Protracted behavior modification, cognitive behavioral therapy, psychological counseling, and mutual support groups have been considered the most effective long-term treatments. Several drugs have been developed that are able to interfere with the neurotransmitters involved in craving mechanisms, and we summarize the evidence of their efficacy to increase abstinence and to prevent relapse.

Conversion from twice-daily to once-daily Tacrolimus administration in liver transplant patient: results of long term follow-up.

OBJECTIVES: The aim of this study was to assess the long term effects of once-daily tacrolimus (OD-TAC) in a cohort of stable liver recipients converted from the twice daily tacrolimus (TD TAC), with a particular attention on the possible effects on renal function. PATIENTS AND METHODS: Between September 2008 and September 2010 conversion from TD-TAC to OD-TAC was proposed in adult stable liver transplant recipients who were followed as outpatients in our Transplant centre. Conversion from TC-TAC to OD-TAC was based on a 1 mg: 1 mg proportion. Tacrolimus through levels, laboratory parameters, metabolic disorders and any adverse events were evaluated at 1, 3, 6, 12 and 24 months after conversion. Renal function was evaluated using creatinine plasma levels and estimated glomerular filtration rate (GFR) derived from the Modification of Diet in Renal Disease (MDRD). Analysis of variance and t test for paired data were utilised for the comparison of the results obtained at the scheduled controls. RESULTS: Sixty-five patients were enrolled in the study (50 males, 15 females, mean age 59±8 years). Median time since liver transplant (LT) was 39 months (range: 6 to 83 months). All patients were followed for a minimum of 12 months. Ninety per cent of patients stabilized their blood levels within 45 days. Liver function, glucose and plasma lipids concentration and arterial blood pressure remained stable during the study. Renal function improved during the 24 months of follow-up. No adverse events or acute rejection episodes were recorded during the study. CONCLUSIONS: Considering the advantage on patient compliance, the equivalent efficacy and the adequate safety of OD-TAC formulation may represent a useful option in liver transplant patients, with a possible advantage on renal function.

Bone disorders in patients with chronic liver disease awaiting liver transplantation.

BACKGROUND: An important complication of chronic liver disease is osteodystrophy, which includes osteoporosis and the much rarer osteomalacia. Both conditions are associated with significant morbidity through fractures resulting in pain, deformity, and immobility. Liver transplantation may further deteriorate bone metabolism. The aim of the present study was to investigate the frequency and severity of hepatic osteodystrophy among patients with liver cirrhosis who were referred for liver transplantation. We also evaluated modifications in bone metabolism after liver transplantation. MATERIALS AND METHODS: We recruited 35 consecutive patients with chronic liver disease who were undergoing assessment for transplantation over a 1-year period. Bone mass in the total skeleton and proximal hip was evaluated using a dual-energy X-ray absorptiometry device (Lunar Prodigy Advance, GE Healthcare, USA). According to World Health Organization recommendations, osteoporosis was defined as a T score < -2.5 and osteopenia as T score between -1 and -2.5. RESULTS: We enrolled in the study 35 patients, including 8 females and 27 males of overall mean age of 57 +/- 7, who showed a viral etiology (57%) or alcohol etiology (28%), Child-Pugh 8.7 +/- 2.3. The overall prevalence of osteodystrophy was 40% (26% osteopenia and 14% osteoporosis). No difference was evident according to gender, severity of liver disease (Child-Pugh, Model for End-stage Liver Disease), or origin of liver disease. A subgroup of 10 transplanted patients reached 3-month follow-up, showing total body T score with a significant decrease after 3 months while femoral T scores tended to decrease insignificantly. CONCLUSIONS: This study revealed a high prevalence of low bone mineral density among cirrhotic patients before liver transplantation. We suggest that both bone mineral density and biochemical examinations should be considered to be routine tests to identify the status of bone mass and bone metabolism among recipients prior to liver transplantation.

Conversion from twice-daily to once-daily tacrolimus administration in liver transplant patient.

BACKGROUND: Compliance to immunosuppressive therapy is critical to prevent organ rejection and possible graft loss. A once-daily Tacrolimus formulation that may improve adherence-to-therapy while allowing the same patient care strategies, total daily dose and monitoring techniques that have been recently approved. The present study was sought to evaluate the feasibility of this formulation among liver transplantation patients (OLT). MATERIALS AND METHODS: Patients transplanted for at least 6 months were enrolled if they had stable doses of Tacrolimus over the last 3 months. Conversion from a twice to a once-daily regimen was based on a 1 mg:1 mg proportion. Tacrolimus blood levels were assessed at 0, 15, 30, 60, 90 days as well and 6 months after conversion. We recorded liver and renal function as well as adverse events. RESULTS: Among twenty-eight patients enrolled in the study including 23 males and 5 females the overall mean age was 59 +/- 8 years and the mean distance from OLT was 39 +/- 22. 32% of patients did not require any dose adjustment. In contrast, 43% required an increase (+0.6 +/- 0.3 mg/d), while 25%, a decrease (-0.5 +/- 0.0 mg/d) in the drug dose to maintain the same tacrolimus blood concentrations as at baseline. Ninety percent of patients stabilized blood levels within 45 days. None of the patients experienced adverse events or alterations in liver function. CONCLUSIONS: Our study confirmed that once-daily Tacrolimus is a useful therapeutic option for OLT patients; however dose adjustments are frequently needed in the short term. The drug is safe and may improve patient compliance.

Adaptation to fatigue of long duration in human wrist movements.

Subjects made fast, accurate, consistent wrist flexions under normal conditions and under conditions of low-frequency fatigue. Movements made 1 h after fatiguing exercise were indistinguishable from those made before exercise, even though twitch tensions were only approximately 60% of their fresh values. Electromyograms (EMGs) recorded from the fatigued muscles were, however, different from those recorded before exercise. EMGs during unfatigued movements showed multiple bursts typical for rapid movements. In the presence of low-frequency fatigue, the duration of the first burst was longer than that under normal conditions, and its onset occurred earlier relative to the initiation of movement. The area of the second agonist burst and, in some cases, the antagonist burst, was increased, although changes in their timings were unclear. We conclude that subjects adapted to low-frequency fatigue by changing the neural patterns controlling their muscles and present a simple model of excitation-contraction coupling that demonstrates how the observed changes in excitation can produce the same kinematics.