Systemic and peritoneal host defense in peritonitis

Most of the work of host defense has been carried out in mixed patient populations. It is now clear that elective preoperative surgical patients have totally different host defense capabilities as compared to posttrauma patients or those suffering from peritonitis. Specific cell-mediated immune studies need to be repeated in these 2 patient groups as well. What will contribute clinical relevance to these studies will be the means to correct the defects. If these defects or—more correctly termed—abnormalities of host defense are, indeed, important and contribute to an increased sepsis rate and mortality from sepsis in affected patients, then correcting them should reduce these complications. This hypothesis can only be tested when such means become available. The issues of most interest in the next few years will be the significance of serum albumin in host outcome, the role of immunomodulators, the involvement of cytokines in the overall process of host defense, and the use of specific nutritional support regimens targeted to the immune system.

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Resumen La mayor parte del trabajo sobre los mecanismos de defensa del huésped ha sido realizada en poblaciones mixtas de pacientes. Actualmente aparece claro que los pacientes preoperatorios electivos poseen una capacidad de defensa de huésped totalmente diferente que la de los pacientes en estado posttrauma o de aquellos con peritonitis. Aparece necesario realizar estudios específicos de inmunidad celular en estos 2 grupos de pacientes; aquello que aporte pertinencia clínica en tales estudios habrá de representar medios para corregir estos defectos. Si tales defectos, mejor denominados anormalidades en las defensas del huésped, son de verdad importantes y contribuyen a mayores tasas de infección y de mortalidad por sepsis en los pacientes afectados, su corrección debe resultar en reducción de estas complicaciones. Esta hipótesis sólo puede ser puesta a prueba cuando tales medios se hallen disponibles. Los aspectos de mayor interés en los próximos años serán el significado de la albúmina sérica en la evolución final del huésped, el papel de los inmunomoduladores, la participación de las citocinas en el proceso general de defensa del huésped, y el uso de regimenes especificos de soporte nutricional dirigidos hacia el sistema inmune.

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Résumé La plupart des travaux sur les mécanismes de défense ont été faits sur les populations mixtes. Il est à présent certain que les patients opérés électivement ont des mécanismes de défense préopératoire totalement différents de ceux des traumatisés ou des patients ayant une infection péritonéale. Les études immunologiques sur la médiation cellulaire spécifique méritent d'être refaites chez ces deux populations. Ce qui ressortira de ces études donnera les moyens de corriger les défauts ou plutôt les anomalies des mécanismes de défense qui contribuent à augmenter septicité et mortalité en rapport avec l'état septique. Cette hypothèse ne peut être vérifiée qu'avec ces moyens. Les questions les plus intéressantes dans les années à venir sera peut-être de connaître l'influence de l'albumine sérique sur l'évolution, le rôle des immunomodulaterus, celui des cytokinines dans le procédé global des mécanismes de défense, et celui de l'utilisation de l'alimentation spécifique pour améliorer le système immune.

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Supported in part by grants from the Medical Research Council of Canada and the Fonds de recherche de Santé.     

Vascularized fibular grafts in the treatment of congenital pseudarthrosis of the tibia

Free vascularized fibular bone grafts were used in nineteen children, seen consecutively, who had congenital pseudarthrosis of the tibia. The average age was 5.1 years (range, 1.4 to 11.4 years). Sixteen of the patients had been treated with electrical stimulation for at least one year, and the tibia had not united. All but four patients had had at least one previous operative procedure. At an average follow-up of 6.3 years (range, 2.0 to 11.0 years), eighteen (95 per cent) of the nineteen pseudarthroses had healed. The leg-length discrepancy averaged 1.6 centimeters (range, 0 to 4.0 centimeters), but ten tibiae had residual or progressive valgus or anteroposterior malalignment despite bracing. There was minimum morbidity at the donor site.     

Assessment of long-term quality of life after laparoscopic and open surgery for Crohn''s disease

OBJECTIVE: Surgery for Crohn's disease (CD) is associated with a high recurrence rate and quality of life (QOL) in these patients is controversial. The aim of this study was to assess QOL in patients after laparoscopic and open surgery for CD by two different validated instruments, a generic nonspecific score and a specific gastrointestinal QOL index. PATIENTS AND METHODS: Patients with CD who underwent elective laparoscopic or open ileocaecal resection with primary anastomosis between 1992 and 2000 were followed for recurrence and surgery-related complications. QOL was assessed by the SF-36 Health Survey containing a mental (MCS) and a physical (PCS) component summary score and by the Gastrointestinal Quality of Life Index (GIQLI) developed by Eypasch. RESULTS: Thirty-seven patients with a mean age of 48.8 +/- 18.4 years including 23 females and 14 males were evaluated at a mean follow-up of 42.6 +/-25.8 months (minimum of 8 months). Twenty-one (57%) patients underwent laparoscopic resection and 16 (43%) open surgery. Both groups were well matched for age, gender, ASA class and body mass index. Fourteen (38%) patients developed recurrent disease and 3 (8%) had postoperative incisional hernias. Overall, QOL scores were 103 +/- 26.8 for the GIQLI, 47.2 +/- 11.8 for the PCS, and 49.2 +/- 11.5 for the MCS. The GIQLI correlated well with the SF36, correlation coefficient = 0.68 for GIQLI vs PCS (95% CI, 0.41,0.95) and 0.67 for GIQLI vs MCS (95%CI, 0.39, 0.95), respectively. When compared to the general US population, mean GIQLI scores (-13.8, P = 0.002) and mean PCS scores (-4.7, P = 0.001) were significantly lower in these patients than in healthy individuals. In a multivariate analysis of impact factors on QOL, recurrence within the follow-up period was the single significant determinant reducing the PCS (-35.1, P = 0.026) and the GIQLI (-36.1, P = 0.018). CONCLUSION: QOL is significantly reduced in patients with CD at long-term follow-up after both laparoscopic and open surgery. Recurrence is the only factor adversely affecting QOL of CD patients in remission irrespective of the operative technique applied.     

Country-specific cost-effectiveness of early intervention with budesonide in mild asthma.

Early intervention with budesonide is an effective strategy for mild persistent asthma, which has been shown to provide additional clinical benefits at a low incremental cost using USA cost data. The present authors analysed whether this strategy would be cost-effective using cost data for other countries. Based on the 3-yr prospective, randomised, double-blind inhaled Steroid Treatment As Regular Therapy (START) in early asthma study (comparing budesonide and placebo combined with usual asthma therapy), the cost-effectiveness was estimated separately for eight different countries, from both healthcare payer and societal perspectives, of adding budesonide to usual asthma therapy. Local unit costs were applied to data for the total trial population. Incremental cost-effectiveness ratios (ICER) were estimated as cost per symptom-free day (SFD) gained. Budesonide increased SFDs by an average of 14.1 days annually. From a healthcare payer perspective, budesonide would reduce the total cost of asthma care in Australia. In Sweden, Canada, France, Spain, UK, China and the USA, the ICER ranged from US$2.4-11.3 per SFD. From a societal perspective, budesonide would be cost-saving in Australia, Canada and Sweden. In conclusion, for countries where costs with budesonide are higher, the policy implication has to be determined by that health system's willingness to pay for an additional symptom-free day. However, where budesonide therapy increases symptom-free days and reduces total costs, the policy conclusion clearly favours early intervention.