Long-term follow-up of patients with alcoholic liver disease after liver transplantation in Sweden: Impact of structured management on recidivism

Objective No systematic evaluation has been performed previously in the Scandinavian countries on patients transplanted for alcoholic liver disease (ALD). Data are limited on the impact of structured management of the alcohol problem on the risk of recidivism following transplantation in ALD.

Material and methods A total of 103 ALD patients were compared with a control group of patients with non-alcoholic liver disease (NALD). The recidivism rates for ALD patients transplanted between 1988 and 1997 as well as after 1998 (institution of structured management) were compared.

Results The median follow-up was 31 (6–60) months in the ALD group and 37 (12–63) months in the control group (NS). The overall survival rates at 1- and 5 years were, respectively, 81% and 69% for the ALD group and 87% and 83% for the non-alcoholic group. The proportion of patients with Child-Pugh C (75%) was higher in ALD patients than in NALD patients (44%) (p<0.01). Thirty-two (33%) ALD patients resumed taking some alcohol after transplantation; 17 patients (18%) were heavy drinkers. A multivariate analysis showed that: sex, age, marital and employment status, benzodiazepine use and a history of illicit drug abuse did not predict the risk of alcohol relapse post-Tx. Nineteen out of 40 (48%) patients transplanted before the start of structured management had resumed alcohol but 13 (22%) out of 58 after this intervention (p=0.002).

Conclusions ALD is a good indication for liver transplantation, with similar results in the ALD patients. Structured management of the alcohol problem before and after transplantation is important in minimizing the risk of recidivism.     

Long-term follow-up of patients with acute liver failure of indeterminate aetiology

Objective. To determine the clinical characteristics of patients with acute liver failure of indeterminate cause and their long-term outcome in comparison with patients with acute liver failure of obvious aetiology (acetaminophen and mushroom poisoning, Budd-Chiari syndrome, acute viral hepatitis) and other controls (idiosyncratic drug reactions, autoimmune hepatitis and Wilson's disease). Material and methods. All patients with acute liver failure and listed for liver transplantation in Sweden between 1984 and 2006 were included in a retrospective analysis. Results. A total of 71 patients with acute liver failure were identified, 33 with indeterminate cause (IDC group), 23 with obvious aetiology (OE group) and 15 other controls (OC group). Before admission to the transplant centre, IDC patients were hospitalized in the referring hospital for 9 days (4–15) versus 1.5 days (1–3) in the OE group (p<0.001) and 7 days (2–14) in the OC group (NS). Serum bilirubin was higher (p<0.001), whereas peak creatinine was lower (p=0.001) in the IDC group compared with the OE group but was not significantly different from the OC group. There were no significant differences in 1-, 3-, 5- and 10-year patient and graft survival rates between the IDC group and the OE or the OC group. Conclusions. Patients with acute liver failure of indeterminate cause seem to differ from those with obvious aetiology in clinical and biochemical presentation but are similar to other controls. The overall long-term outcome seems to be similar in patients with an unknown aetiology as in those with a specific aetiology.     

Plasma levels of granzyme B are increased in patients with lipid-rich carotid plaques as determined by echogenicity

Increased echolucency of carotid plaques is associated with an increased risk of ischemic stroke. Inflammation and apoptosis of vascular smooth muscle cells in the arterial wall are involved in the atherosclerotic process and destabilization of the plaque. Granzyme B (GrB) is a key mediator of T cell-mediated cytotoxicity, and we therefore hypothesized that this protease could distinguish echolucent from other plaques. Ultrasound-determined echolucency of atherosclerotic plaques was assessed prior to carotid endarterectomy/angioplasty in 57 consecutively recruited patients with high-grade internal carotid stenosis. Plasma levels of GrB were measured by enzyme immunoassay prior to surgery. Patients with carotid atherosclerosis had significantly higher plasma levels of GrB compared to healthy controls (n=16) (p<0.01), with particularly high levels in those with an echolucent lesion. While there were no differences in traditional cardiovascular risk factors or CRP between those with echolucent (n=16) and those with echogenic/heterogeneous (n=41) plaques, the echolucent group had markedly raised plasma levels of GrB (p<0.01). Patients with high levels of circulating granzyme B also had more ischemic lesions on cerebral MRI prior to surgery. Raised plasma levels of GrB in echolucent carotid plaques with increased frequency of cerebrovascular events suggest that GrB may be a marker of plaque instability.     

Impact sibutramine therapy in children with hypothalamic obesity or obesity with aggravating syndromes

OBJECTIVE: Behavioral treatment of children suffering from hypothalamic obesity or uncomplicated obesity in combination with syndromes that aggravate this condition has proven to be ineffective. The combination of comorbidities and severe obesity lower the quality of these children's lives drastically. The present goal was to determine whether treatment with sibutramine has a beneficial effect on such children. DESIGN AND SUBJECTS: A double-blind, placebo-controlled, cross-over study (20 + 20 wk), followed by a 6-month open phase, was performed. The primary indicator of efficacy was the body mass index (BMI) sd score (SDS) value, which was analyzed using an ANOVA repeated-measures design [intention to treat (ITT)]. The 50 children (7-20 yr of age) involved included 22 with hypothalamic obesity and 28 with uncomplicated obesity plus aggravating syndromes. Forty-five patients completed the first phase, and 42 participated in the entire study. RESULTS: The group that initially received the placebo demonstrated an insignificant decrease (-0.06) in BMI SDS during this treatment but a significant decrease (-0.68; P < 0.001) when treated with sibutramine. The other group demonstrated a reduction in their BMI SDS of -0.72 during administration of sibutramine and a rebound of +0.43 when placed on the placebo (P < 0.001 in both cases). The response of children with hypothalamic obesity was also significant but was less pronounced than that of children with nonhypothalamic obesity. During the open phase, a continuous reduction in weight was observed. The treatment was tolerated well. CONCLUSION: The clinically and statistically significant weight reduction caused by sibutramine in this short-term study indicates that treatment of hypothalamic and syndromal obesity with this drug may be beneficial.     

Loco-regional Recurrence from Colon Cancer: A Population-based Study

Background The survival after colon cancer surgery has not improved to the same extent as after rectal cancer treatment and studies on loco-regional recurrence after colon cancer surgery are scarce. The aim of this study was to assess the problem of loco-regional recurrence after potentially curative resections for colon cancer, regarding incidence, risk factors, management, and outcome. Methods All 1,856 patients submitted to potentially curative surgery for colon cancer in the Stockholm/Gotland region in Sweden between 1996 and 2000 were followed until January 2005 or until death. Follow-up data were prospectively collected. Risk factors for loco-regional recurrences were analyzed, treatment and outcome for patients with recurrence was studied. Results The cumulative 5-year incidence of loco-regional recurrence was 11.5%. Tumor locations in the right flexure and in the sigmoid colon, bowel perforation and emergent surgery were identified as independent risk factors for loco-regional recurrence. The risk also increased with increasing T- and N-stage. The median survival for all 192 patients with loco-regional recurrence was 9 months. Surgery was performed in 110 (57%) patients. In 23 (12%) patients a complete tumor clearance was achieved and the estimated 5-year survival in this group was 43%. Conclusion Loco-regional recurrence from colon cancer is a significant clinical problem. A multidisciplinary treatment approach, including preoperative staging, a complete resection of the recurrence and more effective adjuvant treatments may improve the outcome.     

Minimally-invasive pediatric surgery in 2004: a survey including 50 German institutions

Background

A survey on the practice of laparoscopic and thoracoscopic surgery in pediatric surgical departments in Germany is presented.

Materials and methods

A questionnaire was sent to all 71 pediatric surgical departments in Germany (population 82 million). Fifty institutions (70%) took part in the survey that mainly included data for the year 2004: spectrum of minimally invasive operations, quantity of procedures, conversions, major complications, number of performing surgeons and residents.

Results

Laparoscopic techniques were used in 48 departments (96%) and thoracoscopic techniques in 37 (74%). The annual frequency of laparoscopies was less than 100 in 30 departments (62%) and more than 100 in 15 (31%). The number of thoracoscopies was less than 50 in 35 departments (73%) and more than 50 in 2 (4%). Appendectomy was offered in 45 (90%), varicocelectomy in 32 (64%), and Fowler-Stephens operation in 33 (66%). Twenty-one departments (42%) covered more advanced procedures such as laparoscopically assisted pull-through for Hirschsprung disease. Most demanding procedures such as laparoscopic choledochal cyst resection, duodeno-duodenostomy, heminephrectomy, or pyeloplasty were offered by 10 departments (20%). Minimally invasive surgery was performed by 1 surgeon (12%) in 6 institutions and by more than 5 surgeons (14%) in 7 institutions.

Conclusion

Minimally invasive techniques are increasingly accepted in most German pediatric surgical institutions for a wide range of indications. However, the number of departments offering major minimally invasive procedures remains limited.     

Objective measurement of fatigue following traumatic brain injury

OBJECTIVES: To quantify posttraumatic brain injury (post-TBI) mental fatigue objectively by documenting changes in performance on neuropsychological tests as a result of sustained mental effort and to examine the relationship between objectively measured mental fatigue and self-reported situational and day-to-day fatigue. PARTICIPANTS: The study included 202 community-dwelling individuals with mild-severe TBI and 73 noninjured controls. MEASURES: Measures included Cambridge Neuropsychological Test Automated Battery, Global Fatigue Index, and situational fatigue rating. METHOD: Subjects were administered a 30-minute computerized neuropsychological test battery 3 times. The second and third administrations of the battery were separated by approximately 2 hours of interviews and administration of self-report measures. RESULTS: The neuropsychological test scores were factor analyzed, yielding 3 subscales: speed, accuracy, and executive function. Situational fatigue and day-to-day fatigue were significantly higher in individual with TBI group than in individuals without TBI and were associated with speed subscale scores. Individuals with TBI evidenced a significant decline in performance on the accuracy subscale score. These declines in performance related to sustained mental effort were not associated with subjective fatigue in the TBI group. While practice effects on the speed and accuracy scores were observed in non-brain-injured individuals, they were not evidenced in individuals with TBI. CONCLUSIONS: Findings were largely consistent with previous literature and indicated that while subjective fatigue is associated with poor performance in individuals with TBI, it is not associated with objective decline in performance of mental tasks.     

Seizures, ataxia, and neuronal loss in cystatin B heterozygous mice

Unverricht-Lundborg disease (EPM1) has been considered to be an autosomal-recessive disease related with loss of function mutations in the gene encoding cystatin B. Although heterozygous carriers are generally asymptomatic, earlier studies in Finnish EPM1 families have reported minor symptoms together with slight changes in the EEG recordings also in near relatives of patients. Here we tested the hypothesis that EPM1 phenotype is expressed also in heterozygous subjects using 17-month-old cystatin B deficient mice as a model of disease. Western blot analysis demonstrated a 50% decrease in cystatin B expression in the cerebellum of these animals. Heterozygous mice showed significantly impaired rotarod performance and were weaker in the grid test. Also the total seizure-rating score of heterozygous animals was higher than in wild-type mice. The stereological analysis revealed a significant decrease in the number of neurons in cerebral cortex and the granule cell layer of cerebellum. These results suggest that partial decrease in cystatin B expression in heterozygous mice could lead to the development of mild EPM1 phenotype.     

Physical activity and headache: results from the Nord-Trøndelag Health Study (HUNT)

The aim of this study was to evaluate, using a prospective and a cross-sectional design, the relationship between level of physical activity and migraine and non-migraine headache. In the prospective part, 22,397 participants, not likely to have headache, answered questions about physical activity at baseline (1984-1986) and responded to a headache questionnaire at follow-up. In the cross-sectional part (1995-1997), 46,648 participants answered questions about headache and physical activity. Physically inactive individuals at baseline were more likely than active individuals to have non-migraine headache 11 years later (odds ratio 1.14, 95% confidence interval 1.02, 1.28). In the cross-sectional analyses, low physical activity was associated with higher prevalence of migraine and non-migraine headache. In both headache groups, there was a strong linear trend (P < 0.001) of higher prevalence of 'low physical activity' with increasing headache frequency. The result may indicate that physical inactivity among headache-free individuals is a risk factor for non-migraine headache and that individuals with headache are less physically active than those without headache.