Increasing liver transplantation waiting list mortality: a report from the Australian National Liver Transplantation Unit, Sydney.

BACKGROUND: We aimed to describe the demand for liver transplantation (LTx) and patient outcomes on the waiting list at the Australian National Liver Transplantation Unit, Sydney over the last 20 years. METHODS: We performed a retrospective analysis with the data divided into three eras: 1985-1993, 1994-2000 and 2001-2008. RESULTS: The number of patients accepted for LTx increased from 320 to 372 and 548 (P < 0.001) with the number of LTx being performed increasing from 262 to 312 and 452 respectively (P < 0.001). The median adult recipient age increased from 45 to 48 and 52 years (P < 0.001) while it decreased in children from 4 to 2 and 1 years respectively (P = 0.001). In parallel, the deceased donor offers decreased from 1003 to 720 and 717 (P < 0.001). Methods to improve access to donor livers have been used with the use of split livers, extended criteria and non-heart beating donors, resulting in increased acceptance of deceased donor offers by 65% and 115% in the second and third eras when compared with the first era (P < 0.001). However, the adult median waiting time has increased from 23 to 41 and 120 days respectively (P < 0.001). This was associated with increased adult mortality on the waiting list from 23 to 40 and 122 respectively (P < 0.001). CONCLUSIONS: Despite the increasing proportion of donor offers being used, the waiting list mortality is increasing. A solution to this problem is an increase in organ donation to keep pace with the escalating demand for LTx.

Guidelines for the management of hospital-acquired pneumonia in the UK: report of the working party on hospital-acquired pneumonia of the British Society for Antimicrobial Chemotherapy.

These evidence-based guidelines have been produced after a systematic literature review of a range of issues involving prevention, diagnosis and treatment of hospital-acquired pneumonia (HAP). Prevention is structured into sections addressing general issues, equipment, patient procedures and the environment, whereas in treatment, the structure addresses the use of antimicrobials in prevention and treatment, adjunctive therapies and the application of clinical protocols. The sections dealing with diagnosis are presented against the clinical, radiological and microbiological diagnosis of HAP. Recommendations are also made upon the role of invasive sampling and quantitative microbiology of respiratory secretions in directing antibiotic therapy in HAP/ventilator-associated pneumonia.

Inferior liver allograft survival from cadaveric donors >50 years of age?

The growing imbalance between the number of cadaveric organ donors and recipients has led to an increasing use of high-risk donors as an option to expand the donor pool. The aim of this study was to evaluate our experience with the use of older liver (donor>50 yr of age) allografts. The medical records, postreperfusion biopsies and laboratory results were reviewed of the 393 patients who underwent orthotopic liver transplantation between 1986 and 1997. The outcome of the 61 patients who received older livers (OL) was compared to that of the other 332 recipients. Increasing use of OL was evident from 1992 onwards. Recipients of OL were older than recipients of younger livers (YL, p<0.001) and more commonly had underlying chronic viral hepatitis (CVH) or fulminant hepatic failure (p<0.05). Patient and allograft survival were only slightly less in recipients of OL versus YL (p=NS). Although postperfusion biopsies showed more damage in OL than YL allografts (p<0.05), this was not associated with increased primary graft failure. OL allografts can be transplanted with acceptable results into recipients without the concern of early allograft loss. SUMMARY OF ARTICLE: This report of one centre's experience with 61 recipients of older donor liver allografts identifies recipient factors that may also have a negative impact on allograft outcome. These factors include a diagnosis of either CVH or fulminant hepatic failure at the time of transplantation. Postreperfusion biopsies of older donor allografts tend to show more damage, but this is not associated with primary non-function.

Pancreatitis in adult orthotopic liver allograft recipients: risk factors and outcome.

Acute pancreatitis (AP) has been described after orthotopic liver transplantation but is uncommon in stable patients after the initial perioperative phase. The aim of this study is to review our experience with AP occurring more than 2 months after primary allografting and determine possible contributing factors plus patient outcome. A review of patient files and the unit database was performed. AP was diagnosed in 9 of 298 patients (3%) on 12 occasions. The incidence of AP was greater in men (8 of 163 men) than women (1 of 135 women; P <.04). Underlying factors to each episode of AP were biliary manipulation (4 of 12 episodes; 33%), history of recent alcohol ingestion (3 of 12 episodes; 25%), and malignancy in the region of the pancreas (2 of 12 episodes; 16%). AP was associated with a diagnosis of either hepatic artery thrombosis combined with biliary tract complications (P <.005) or malignancy (P <.004). In 7 of 12 episodes of AP (58%), conservative management alone was successful. In 3 of 9 patients (33%), subsequent surgery was required. One patient died of pancreatic malignancy. In conclusion, AP is uncommon in stable liver transplant recipients. Male sex, complications of hepatic artery thrombosis, and malignancy in the region of the pancreas are associated with AP in this study.

Mortality and rebleeding following Transjugular Intrahepatic Portosystemic Stent Shunt for variceal haemorrhage.

The present study investigates clinical factors associated with decreased survival following Transjugular Intrahepatic Portosystemic Stent Shunt (TIPSS). Sixty-seven patients underwent TIPSS for bleeding related to portal hypertension, 42 (63%) on an urgent basis. TIPSS was successfully placed in 65 (97%) patients with no fatal procedural complications. Thirty day mortality was 21%, there being several predictive factors: transfer from another institution, urgency of procedure, sepsis, encephalopathy, higher mean serum bilirubin and low serum albumin. However, using regression analysis, 30 day mortality was predicted independently only by severe liver disease (Child-Pugh C, P= 0.003) and older age (P= 0.003). When stratified by Child-Pugh class, cumulative survival rates at 1 year for class A, B and C were 100, 90 and 34%, respectively. Only three of 25 patient deaths were due to variceal rebleeding. Thirty (46%) patients had a total of 41 rebleeding episodes, with mean time to first rebleed of 4.8 months (range, 3 days-38 months). Cumulative rebleeding rate at 1 year was 25%. Log-rank analysis did not reveal a significant difference in overall survival between rebleeders and non-rebleeders (P= 0.125). When investigated, shunt abnormalities (stenosis, occlusion) were identified in all cases of rebleeding. Our findings confirm TIPSS can be safe and effective in the control of refractory variceal haemorrhage. However, prognosis remains poor for patients with advanced liver disease, particularly if older and in the emergency setting. Vigilant surveillance and high rate of intervention is necessary to maintain shunt patency. Consideration could be given to elective shunt surgery instead of TIPSS for patients with recurrent bleeding and good prognosis liver disease.

Thalidomide reduces tumour necrosis factor-alpha production by human alveolar macrophages.

Overexuberant production of tumour necrosis factor-alpha (TNF-alpha) by macrophages and other cells is thought to contribute to the development of permanent lung damage in many inflammatory conditions. There is a need for an agent, without the side-effects of corticosteroids, which can reduce the production of TNF-alpha by macrophages activated by disease. This study evaluated the effect of thalidomide on lipopolysaccharide (LPS)-induced TNF-alpha production by human alveolar macrophages obtained from patients with tuberculosis and a group of other diseases associated with macrophage activation. Alveolar macrophages obtained by bronchoalveolar lavage from 31 patients (tuberculosis = 12, sarcoidosis = 3, lung cancer = 5, chronic bronchitis = 5, pneumonia = 6) were stimulated with LPS alone or LPS in combination with either thalidomide or dexamethasone. Cell-associated TNF-alpha, as measured by immunochemistry, and TNF-alpha released by macrophages, as assessed by ELISA, were markedly increased when cells were incubated with LPS (P < 0.05), and both were decreased following addition of thalidomide (P < 0.05) or dexamethasone (P < 0.05) to amounts similar to those observed when macrophages were incubated with medium alone. Similarly, TNF-alpha mRNA as measured by in situ hybridization was increased following incubation with LPS (P < 0.05), but this increase was prevented by addition of thalidomide (P < 0.05) or dexamethasone (P < 0.05). The ability of thalidomide to reduce LPS-induced TNF-alpha production by alveolar macrophages was the same when cells from patients with tuberculosis (a disease associated with TNF-alpha production) and cells from patients with the other conditions were compared. The ability of thalidomide to reduce TNF-alpha production by human alveolar macrophages from patients with active lung disease suggests that thalidomide and its analogues may have potential as drugs to reduce TNF-alpha production in disease.

Hypothalamic-pituitary adrenal function in end-stage non-alcoholic liver disease.

Patients with end-stage liver disease have significant mortality often associated with intercurrent episodes of bleeding or sepsis. Intact adrenal function is essential in such situations. In order to test the hypothesis that adrenal insufficiency might be present in severe liver disease, hypothalamic-pituitary adrenal function was evaluated in patients with end-stage liver disease awaiting transplantation. The study had a prospective, open comparative design with patients restricted to those having non-alcoholic liver disease in order to avoid the confounding direct effects of alcohol on adrenocortical function. Fifty-one consecutive patients with end-stage, non-alcoholic liver disease undergoing evaluation for liver transplantation and 40 healthy controls were studied. Patients who had used corticosteroids (n = 8) or who were unable to complete the investigations (n = 5) were excluded leaving 38 patients eligible for analysis. Adrenal function was evaluated under basal conditions by single morning measurements of plasma total and free cortisol, corticosteroid-binding globulin, dehydroepiandrosterone sulfate and by adrenal stimulation indirectly using insulin-induced (0.1 U/kg, i.v.) hypoglycaemia and/or directly by adrenocorticotrophic hormone (ACTH); 250 micrograms tetracosactrin, i.v.) stimulation. Compared with healthy controls, patients with liver disease had a 64% reduction in maximal increments of plasma cortisol to indirect adrenal stimulation via insulin-induced hypoglycaemia and a 39% reduction to direct adrenal stimulation by ACTH (all P < 0.001). There was a significant negative correlation between the severity of underlying liver disease as assessed by Child-Pugh scores and peak control responses to ACTH (r = -0.647, P < 0.0001) and insulin-induced hypoglycaemia (r = -0.597, P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Bone loss after liver transplantation.

We studied 35 adult patients (mean age = 43 yr) referred for orthotopic liver transplantation. Spinal bone mineral density was measured by quantitative computed tomography scanning before transplantation (n = 35) and at 3 mo (n = 21) and 12 mo (n = 11) after orthotopic liver transplantation. The readings were corrected to age 50 yr, using the regression equations derived from normal control subjects. Quantitative bone histological studies were performed in 17 patients before orthotopic liver transplantation and 3 mo after orthotopic liver transplantation. Before orthotopic liver transplantation, the corrected spinal bone mineral density in men was 108 +/- 20 mg/cm3, less than in male control subjects (129 +/- 22 mg/cm3, p less than 0.005). In women patients the value was 117 +/- 27 mg/cm3, and in female control subjects 126 +/- 19 mg/cm3 (NS). However, women patients with primary biliary cirrhosis had lower spinal bone mineral density (106.5 +/- 14.8) than female control subjects (p less than 0.005). Histologically, the resorbing surface was near the normal mean, whereas the osteoblast surface, tetracycline surface and bone formation rate was lower in men (p less than 0.05) but not women. Spinal bone mineral density decreased by 24% in the first 3 mo after orthotopic liver transplantation with no further decrease at 12 mo. Five patients had vertebral fractures within 6 mo of orthotopic liver transplantation. One patient fractured a wrist and three had osteonecrosis of the hip or knee.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of station examination item sampling on generalizability of student performance.

This article may be of interest to physical therapy educators who are responsible for structuring station or practical examinations used to evaluate physical therapy students. The global intent of the article is to provide information that may be useful in selecting test items. Specifically, the purposes of this study were 1) to examine how two item-sampling strategies (one based on different diagnostic concepts, or diagnostic probes, and the other based on different anatomical sites) influenced the generalizability of a station examination, 2) to determine the interrater reliability during the station examination, and 3) to determine whether the status of the rater (that of observer or simulated patient) influenced the rating. Using a nested study design, 24 physical therapy students were assessed by eight raters. The raters were randomly and equally assigned to four teams. Each team assessed six students. One rater acted as the simulated patient for the first three students in each group, and the other rater acted as observer. This order was reversed for the last three students. Each student performed nine mini-diagnostic patient cases consisting of three diagnostic probes reproduced at three different anatomical sites. The results demonstrate that 1) similar diagnostic concepts can be generalized across anatomical sites, although different concepts or skills cannot be generalized at a given anatomical site or across sites; 2) interrater reliability was excellent; and 3) the status of the raters (ie, simulated patient or observer) did not bias the ratings.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of smoking on the recurrence of malignant melanoma.

Smoking has been recently shown to lead to aberrant immunological function in man. Since immunological host resistance is important in the natural history of human malignant melanoma, it was the object of this study to determine the effects of smoking on the course of this disease. Investigations on 1908 patients with malignant melanoma indicated that smoking renders men significantly more susceptible to developing metastases. The proportion of men smokers free of disease five years after melanoma diagnosis was significantly lower than that of men non-smokers. An effect of smoking similar to that recorded in men was not evident in women with malignant melanoma.