Selective Use of Older Adults in Right Lobe Living Donor Liver Transplantation

Many centers are reluctant to use older donors (>44 years) for adult right-lobe living donor liver transplantation (RLDLT) due to concerns about possible increased morbidity in donors and poorer outcomes in recipients. Since 2000, 130 adult RLDLTs have been performed at our institution. Recipients were divided into those who received a right lobe graft from a donor ≤age 44 (n = 89, 68%; median age 30) and those who received a liver graft from a donor age >44 (n = 41, 32%; mean age 52). The two donor and recipient populations had similar demographic and operative profiles. With a median follow-up of 29 months, the severity and number of complications in older donors were similar to those in younger donors. No living donor died. Older donor allografts had initial allograft dysfunction compared to younger donors. Complication rates were similar among recipients in both groups but there was a higher bile duct stricture rate with older donor grafts (27% vs. 12%; p = 0.04). One-year recipient graft survival was 86% for older donors and 85% for younger donors (p = 0.95). Early experience with the use of selected older adults (>44 years) for RLDLT is encouraging, but may be associated with a higher rate of biliary complications in the recipient.     

A blinded, randomized, multicenter study of an intravenous Staphylococcus aureus immune globulin.

OBJECTIVES: Very low birth weight (VLBW) infants are vulnerable to nosocomial infections and subsequent morbidity; including infections caused by Staphylococcus aureus: 85% of nosocomial S. aureus infections are caused by capsular polysaccharide (CPS) types 5 and 8. Altastaph is a polyclonal investigational human immunoglobulin G (IgG) with high levels of opsonizing S. aureus CPS types 5 and 8 IgG. METHODS: A Phase 2 clinical trial to assess the safety and kinetics of Altastaph in VLBW infants. Neonates in this multicenter study were randomized to receive two identical 20 ml/kg i.v. infusions of either 0.45% NaCl placebo or 1000 mg Altastaph/kg. Each infant was followed for 28 days after the second infusion or until discharge. Serum S. aureus CPS types 5 and 8 IgG levels were measured preinfusion and at various times after each infusion. RESULTS: Of 206 neonates, 158 received both infusions. Adverse events were similar in the two treatment groups. Six subjects (3% in each group) discontinued owing to an adverse event. Geometric mean anti-type 5 IgG levels were 402 and 642 mcg/ml 1 day following infusion of the first (day 0) and Second (day 14) doses, respectively, in neonates < or =1000 g and slightly higher in neonates 1001 to 1500 g. Trough levels before second infusion were 188 mcg/ml. Type 8 IgG levels were similar. Geometric mean IgG levels among placebo recipients were consistently <2 and <5 mcg/ml for types 5 and 8 in both weight groups. Three episodes of S. aureus bacteremia occurred in each arm. CONCLUSIONS: Infusion of Altastaph in VLBW neonates resulted in high levels of specific S. aureus types 5 and 8 CPS IgG. The administration of this anti-staphylococcal hyperimmune globulin was well tolerated in this population.     

Inhibition of interleukin-8 expression by dexamethasone in human cultured airway epithelial cells.

Interleukin-8 (IL-8) is a neutrophil chemotactic factor expressed in many cell types, including human airway epithelial cells (HAEC). Inhaled corticosteroids are now used increasingly early in the treatment of airway inflammation such as in asthma, and directly interact with HAEC at relatively high concentrations. We have investigated the effect of dexamethasone on IL-8 expression in primary cultured HAEC obtained from transplantation donors. Northern blot analysis was used to measure IL-8 mRNA levels in HAEC, and radioimmunoassay was used to measure IL-8 protein in culture supernatant fluids. We demonstrated that IL-8 was expressed by primary cultured HAEC and that this was enhanced by IL-1 beta and tumour necrosis factor-alpha stimulation, but not by IL-6 or lipopolysaccharide. Dexamethasone suppressed IL-8 mRNA expression and protein synthesis dose-dependently in both resting and stimulated HAEC. The half-life of IL-8 mRNA determined in the presence of actinomycin D was less than 1 hr, and dexamethasone preincubation had no effect on mRNA stability. These results support the view that HAEC may play an important role in the pathogenesis of airway inflammatory diseases, and that glucocorticosteroids may exert their anti-inflammatory effects by blocking IL-8 gene expression and generation in these cells.     

Sputum microbiome profiles identify severe asthma phenotypes of relative stability at 12 to 18 months

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Nitrosative stress in the bronchial mucosa of severe chronic obstructive pulmonary disease

BACKGROUND: Reactive nitrogen species, formed via the reaction of nitric oxide (NO) with superoxide anion and via (myelo)peroxidase-dependent oxidation of NO(2)(-), have potent proinflammatory and oxidizing actions. Reactive nitrogen species formation and nitrosative stress are potentially involved in chronic obstructive pulmonary disease (COPD) pathogenesis. OBJECTIVES: To investigate the expression of markers of nitrosative stress, including nitrotyrosine (NT), inducible NO synthase (iNOS), endothelial NO synthase (eNOS), myeloperoxidase (MPO), and xanthine oxidase (XO) in bronchial biopsies and bronchoalveolar lavage from patients with mild to severe stable COPD compared with control groups (smokers with normal lung function and nonsmokers). METHODS: The expression of NT, iNOS, eNOS, MPO and XO in the bronchial mucosa and bronchoalveolar lavage of patients was measured by using immunohistochemistry, Western blotting, and ELISA and correlated with the inflammatory cell profile. RESULTS: Patients with severe COPD in stable phase had higher numbers of NT(+) and MPO(+) cells in their bronchial submucosa compared with mild/moderate COPD, smokers with normal lung function, and nonsmokers (P < .01). iNOS(+) and eNOS(+) but not XO(+) cells were significantly increased in smokers with COPD or normal lung function compared with nonsmokers (P < .05 and P < .01, respectively). In patients with COPD, the number of MPO(+) cells was significantly correlated with the number of neutrophils (r = +0.61; P < .0025) in the bronchial submucosa. Furthermore, the number of NT(+) and MPO(+) cells was negatively correlated with postbronchodilator FEV(1). CONCLUSION: These data suggest that nitrosative stress, mainly mediated by MPO and neutrophilic inflammation, may contribute to the pathogenesis of severe COPD.     

Emergency department thoracotomy (EDT). A 26-month experience using an "agonal" protocol

EDT can be successfully performed with the proper system in place. This includes an established thoracotomy protocol, a well-integrated EMS system, and an in-house team. Time seems to be critical, and the time between injury and EDT may be the single most important factor affecting survival other than the mechanism of injury. Cardiac penetrations, especially stab wounds, were found to have a 93 per cent survival while subdiaphragmatic penetrations had only one survivor from a group of 18 patients (5.5%). The high rate of salvage in the heart wound group probably reflects the speed of prehospital transport, though all other major series have found this group to gain the maximum benefit. No patient was successfully resuscitated from blunt injury with EDT. Three additional patients had "signs of life" restored (one pediatric blunt; two subdiaphragmatic gunshot wounds) but died of coagulopathies shortly thereafter. The experience with air ambulance patients was far too small to allow any conclusions or observations. It is felt that as the use and application of helicopters to EMS situations becomes widespread, more patients will be arriving at trauma centers with no vital signs and massive blunt injury but only moments from the accident. This special group of "dying" patients will require intense scrutiny and possibly new and inventive approaches for any hopeful salvage. Emergency thoracotomy will, no doubt, have a place as part of this. The development of a simple working protocol is of extreme importance. The protocol should be one that will allow maximum selection of patients who can benefit and elimination of those patients where EDT would be useless. The primary benefactor for EDT remains the patient sustaining a stab wound to the heart who arrives at the center shortly after injury. In other areas, such as abdominal exsanguination or severe blunt injury, further study is needed to determine what factors, prehospital and resuscitative, will improve outcome.