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The onset of local and systemic inflammatory effects in secondary peritonitis is usually closely related to the presence of many inflammatory mediators such as cytokines. The main purpose of this paper is to review the mechanisms induced by secondary peritonitis related to the production of cytokines, to determine their role in the onset of local inflammatory responses and in the onset of systemic inflammatory responses leading to multiple organ failure. We also review the immunomodulatory effects induced by cytokine production and their counteraction. Finally we analyze the potential therapeutic effects of cytokine-related drugs and their role in the management of patients with secondary peritonitis and systemic inflammatory response syndrome. In this regard the following substances are important: nonspecific immunomodulators, anti-cytokine antibodies, and inhibitors of the cytokine effect and of adhesion molecules.

Introduction EuroTransplant old-to-old program allows patients older than 60 years to receive offers from donors older than 60. The long-term results of kidney transplantation in this model are still under discussion, due to the impaired kidney function of the donor and cumulative diseases in the recipient. Hypothesis Calcineurin-sparing protocols with IL-2 antibody induction (Simulect) may benefit long-term kidney function in these patients avoiding overimmunosuppression. The main outcome measures are: graft function and rejection rate during the first year after transplant. Patients and methods A cohort of 15 consecutive older subjects were prospectively compared with 30 conventional cadaveric kidney transplants. Study patients were induced with Simulect (20 mg, 30 minutes before reperfusion and 4 days after transplantation) and steroids allowing the introduction of CsA to be delayed to the time at which the creatinine is below 3 mg/dL. Conventional patients were immunosuppresed with Tacrolimus (trough 8–12 ng/mL), MMF (1 g/d) and identical steroid tape. The graft and patient survival, kidney function in terms of diuresis, creatinine clearance, rejection episodes and grades were compared between both groups during the first year posttransplantation. Results Except for the age of the donors and recipients in both groups (72 vs 54 in donors, and 67 versus 52 years in recipients), no significant differences were observed. Patient survival rates were 97% in control patients and 100% in the Simulect group. Graft survival was 97% in the control group and 100% in the old-to-old study group. Acute rejection episodes were decreased among study patients (6.6% vs 13.2%), and corticoid sparing protocols were applied in 75% of Simulect patients but only 50% of control patients. All 44 patients and grafts showed excellent kidney function after one year with equal creatinine levels in both groups (mean 1.42). Conclusions Calcineurin free protocols with IL-2 therapy as the main initial suppression allows patients in an old-to-old ET program to have superior results to conventional cadaveric kidney transplants.

Introduction Markov models are employed in economic analyses to evaluate all possible expectations in a dilemna. The introduction of a new clinical protocol (Basiliximab induction with calcineurin-sparing protocols) for a group of kidney transplant recipients receiving organs from marginal donors was validated with a Markov simulation model, demonstrating the usefulness of combining simulation with Bayesian estimation methods for analysis of cost-effectiveness data collected alongside a clinical trial. We sought to determine whether calcineurin-sparing protocols using anti-interleukin-2/antibody induction (Simulect) would show a beneficial effect on initial kidney function and reduce transplantation costs upon admission, clinical incidences, graft function, and complications during the first month after transplant. Patients and methods A Markov Chain Monte Carlo (MCMC) was used to estimate a system of generalized linear models relating costs and outcomes to a kidney transplant process affected by treatment under alternative therapies. The Markov simulation model was established following three chains: a calcineurin-free regimen with Basiliximab induction (chain A); a calcineurin-sparing protocol with Basiliximab induction (chain B); and a conventional immunosuppressive regimen (chain C). The MCMC draws were used as parameters in simulations that yielded inferences about the relative cost-effectiveness of the novel therapy under a variety of scenarios. After designing the Markov chain and cohorts, 31 patients from the “old-to-old” program were assigned; eight to chain A; eight to chain B; and 15 to chain C. A year after transplantation a cost-benefit study was performed guided by the three branches of the Markov model. Results The Markov model showed a benefit of induction therapies in elderly patients. A cost-benefit model showed that after a year, there was a clear benefit from calcineurin-free plus Basiliximab induction therapies, with a slight benefit from calcineurin-sparing protocols. Conclusions Markov models are extremely useful when introducing new clinical therapies. The approach allows flexibility in assessing treatment using various premises and quantifies the global effect of parametric uncertainty on a decision maker’s confidence to adopt one therapy over another. In our transplant program, a cost-effective analysis of outcomes in old patients using the Markov model showed a clear benefit of calcineurin-sparing protocols with Basixilimab induction.

Introduction The EuroTransplant “old to old” program establishes that patients older than 60 years can receive offers of organs from donors older than 60 years. The compromised function of these organs makes it a priority to preserve their initial kidney function. Hypothesis Calcineurin-sparing protocols using anti-IL-2 receptor (IL-2R) antibody induction (Simulect) may benefit initial kidney function in these patients, as assessed by the rates of delayed graft function and of rejection during the first month after transplant. Patients and methods A cohort of 15 consecutive elderly patients were prospectively compared with 30 cadaveric kidney transplants in younger recipients. Study patients were induced with Simulect (20 mg, 30 minutes before reperfusion and 4 days after transplantation) and steroids, delaying the introduction of CsA until the serum creatinine was below 3 mg/dL. The other cohort of patients were immunosuppressed with tacrolimus (trough 8 to 12), mycophenolats mofetil (MMF, 1 g/d), and an identical taper of steroids. The analysis compared donor and recipient ages, mean cold ischemic time, incidence of initial kidney function (diuresis in the first 24 h) serum creatinine levels, glomerular filtration rate (GFR), number of dialysis sessions, and rejection rate in the two groups. Results Except for the donor and recipient ages (72 vs 54 in donors, and 67 versus 52 years in recipients), no significant differences were observed between the groups among the rates of acute rejection (6.6% vs 13.2%), delayed graft function (13.2% required dialysis), or infection (6.6%). Within 1 month all 45 grafts showed primary function with equal creatinine levels (mean 1.65). Conclusions Calcineurin-free protocols using IL-2 therapy as the initial suppression allow patients in the “old to old” ET program to display equal results to cadaveric kidney transplants with initial treatment with calcineurin antagonists.

Introduction Markov models are employed in economic analyses to evaluate all possible expectations in a dilemna. The introduction of a new clinical protocol (basiliximab induction with calcineurin-sparing protocols) for a group of kidney transplant recipients receiving organs from marginal donors was validated with a Markov simulation model. Hypothesis Calcineurin-sparing protocols using anti-IL-2/antibody induction (Simulect) show a beneficial effect on initial kidney function, reducing transplantation costs reception based upon mean length of stay, mean admission cost, and incidences of delayed graft function and complications during the first month after transplant. Patients and methods A Markov simulation model was established following three different chains. A calcineurin-free regimen with basiliximab induction (chain A), a calcineurin-sparing protocol with basiliximab induction (chain B), and a conventional immunosuppressive regimen (chain C). After designing the Markov chain and cohorts, 31 patients from the “old to old” program were assigned to each chain eight to chain A, (eight to chain B, and 15 to chain C). A month after transplantation a cost-benefit study was performed guided by the three branches of the Markov model. Results The Markov model showed a benefit of induction therapies in elderly patients. A cost-benefit model showed that after a month there was a clear benefit from Calcineurin=free plus basiliximab induction therapies, with a slight benefit from calcineurin-sparing protocols. Conclusions Markov models are extremely useful when introducing new clinical therapies. In our transplant program, a cost-effective analysis of outcomes in old patients using the Markov model showed a clear benefit of calcineurin-sparing protocols with basixilimab induction.

Background: Acute abdominal pain due to complicated Meckel’s diverticulum is an unusual event. Even the presence of biliary enterolithiasis at the onset of inflamed congenital diverticulum has rarely been reported previously. Results: Despite this unusual presentation, an episode of gallstone passage through the biliary tract has not yet been described. Conclusions: Whether the stones were primarily formed in the diverticulum as enterolithiasis, or secondary to gallstone passage is discussed. The complications of Meckel’s diverticulum requiring surgical treatment are reviewed, focusing on the unusual finding of biliary stones in Meckel’s diverticulum and the etiogenic mechanism of enterolithiasis.

Surgical procedures on patients with severe immune deficiencies are increasing. The fact that an immunocompromised state is a major factor in the pathogenesis of infection makes it imperative that the clinician has an adequate working knowledge of the host’s antibacterial defense systems and how they are affected by surgery.

Background Fungal infection is a devastating complication with an increased incidence in the past decade. Immune-depressed patients undergoing high-risk procedures have an increased incidence of surgical infection, particularly due to fungal colonization. Methods Twenty patients undergoing pancreas transplantation, 20 kidney transplant patients undergoing biliary tract surgery, 20 patients with human immunodeficiency virus (HIV) undergoing biliary tract surgery and 20 patients undergoing pancreatic resection for neoplasms were enrolled in a prospective study concerning perioperative surgical infection. All patients underwent surgical procedures by the same surgeon. All had preoperative blood counts, assay of CD lymphocyte populations, complete nutritional evaluation and similar antibiotic prophylaxis. Perioperative care was done to a similar standard and only patients undergoing pancreas transplantation received fungal prophylaxis (nystatin wash and swallow). In patients with clinical signs of infection, cultures were sent with special consideration to fungal infection. Results Two of the patients undergoing pancreas transplantation (one of whom died from disseminated candidiasis), three of the kidney transplant patients (two on the wound, one in the catheter), three patients with HIV (two on bile culture, one in the bloodstream) and one of the patients undergoing pancreatic resection (pancreatic fistula and bloodstream) had fungal infection. All patients had concomitant bacterial infections at the time of fungal infection (60 per cent Staphylococcus epidermidis). Patients with fungal infection had increased levels of immunosuppression with decreased CD4 recounts (pancreas transplants and patients with HIV), increased perioperative levels of blood glucose requiring insulin treatment, prolonged antibiotic therapy with broad-spectrum antibiotics (piperacillin–tazobactam), previous positive cultures from the bile of the biliary tract or the duodenum of the transplanted pancreas, and concomitant bacterial infections (especially opportunistic). Conclusion Surgical patients with positive cultures from surgical specimens, prolonged broad-spectrum antibiotic therapy and severely decreased lymphocyte immune function had an increased incidence of fungal infection with significant morbidity and mortality rates. Fungal prophylaxis is strongly recommended in these high-risk patients undergoing biliopancreatic tract surgery.

Background In previous studies the authors have selected patients and surgical procedures with a high risk of fungal infection. Whether these patients and procedures require fungal prophylaxis was studied. Methods From June to December 1999, 850 surgical patients from two university hospitals were enrolled in a prospective open randomized study. Fifty were selected according to demographics (age, sex, co-morbidity) and surgical procedures (defined by GDRs and ICD9-CM) as at high risk of fungal infection according to a previously defined algorithm (presented to the Surgical Infection Society of Europe 1999). In these 50 patients the CD lymphocyte population was recollected, and urine, blood, sputum and wound (if infected) cultures were performed. Then, 25 were treated with nystatin wash and swallow, and the others with placebo. Fungal infection and fungal colonization were defined and used as the endpoint of the study. Results Patients not selected for the study did not develop fungal infection. Of the high-risk patients, 20 presented with fungal colonization (12 urine, seven wound and five bloodstream cultures) and 12 presented with subsequent fungal infections. Of these 20 colonized patients, only those with nystatin prophylaxis did not require fungal treatment, whereas controls required treatment. CD4 lymphocyte recount (below 300) was uniformly decreased in all patients with fungal infection. Conclusion Immunodepressed patients at high risk with concomitant fungal colonization develop fungal infections 2–5 days after high-risk surgical procedures. Nystatin prophylaxis in such patients may reduce the degree and severity of fungal infection. If fungal colonization is present and the CD4 lymphocyte count is below 300, fungal treatment might be advisable.

A striking pancreatic juice reflux toward the biliary tree (PR) has frequently been found in subjects with common bile-pancreatic conduit (CBPC) and gallstone-induced acute pancreatitis (SAP). Our aim was to determine the role of the CBPC functional diameter as a potential trigger of PR. The CBPC was calibrated in three groups of patients: (A) patients with gallbladder stones using intraoperative direct cholangiometry (n = 24), (B) patients after surgical removal of common bile duct stones using postoperative cholangiometry via T-drain (n = 6), and (C) patients with SAP using the same procedures as in group B (n = 6). In all patients in groups B and C, aliquots of bile were collected and assayed for pancreatic amylase content. The mean functional diameter of the CBPC varied from 0.80 mm in patients in groups A and B to 0.47 mm in group C (p < 0.001). The bile samples of group B contained low concentrations of amylase, whereas high values could be found in all samples of group C. We conclude that PR is a frequent event occurring after bile duct revision concerning small amounts of pancreatic juice. However, CBPC functional stenosis as seen in patients with SAP obviously induces PR with high amounts of pancreatic juice.