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Azathioprine maintains long-term steroid-free remission through 3 years in patients with steroid-dependent ulcerative colitis.

Background: Studies assessing the efficacy of azathioprine (AZA) in steroid‐dependent ulcerative colitis (SD‐UC) are scarce. The purpose of this trial was to explore the efficacy of AZA in maintaining steroid‐free remission in SD‐UC patients and the factors associated with sustained response. Methods: In this observational cohort study, 42 subjects with SD‐UC were recruited for AZA therapy during a 3‐year period. AZA was adjusted for a target dose of 2–3 mg/kg/day. Steroid therapy was tapered off following a standardized regimen. The primary endpoint was the annual rate of steroid‐free response to AZA. Secondary endpoints included clinical recurrence, yearly steroid dose, and safety of treatment. Results: On an intention‐to‐treat basis, the proportion of patients remaining in steroid‐free remission at 12, 24, and 36 months was 0.55, 0.52, and 0.45, respectively. A significant decrease in the flare‐ups rate and in requirement for steroids were observed during 3 years on AZA compared with the previous year (P = 0.000 for both). Patients with and without sustained response were comparable according to demographics, extent of disease, dose of AZA, steroids, and 5‐aminosalicylate (5‐ASA) use. Only disease duration <36 months was associated with off‐steroids remission (P = 0.02, odds ratio [OR] 3.12, 95% confidence interval [CI] 1.89–7.64). The AZA benefit‐risk profile was favorable. Conclusions: In this open‐label observational trial AZA showed sustained efficacy for maintenance of clinical remission off steroids and steroid sparing through 3 years of therapy in SD‐UC. Patients with earlier UC are those who most probably will have sustained steroid‐free remission at the end of 12 months while on AZA. Inflamm Bowel Dis 2009

A full solid diet as the initial meal in mild acute pancreatitis is safe and result in a shorter length of hospitalization: results from a prospective, randomized, controlled, double-blind clinical trial.

Goals To compare the safety and length of hospitalization (LOH) between a full solid diet as the initial meal for refeeding after mild acute pancreatitis (AP) as compared with 2 other diets. Background In mild AP, the need for fat restriction during refeeding has not been studied. It was hypothesized that the reintroduction of oral feeding with a full solid diet after mild AP was safe and might result in a shorter LOH. Study Subjects with mild AP were randomized to receive 1 of 3 diets (clear liquid, soft, or full solid) as the initial meal during oral refeeding. Diet progression and hospital discharge were decided by the physicians that were not members of trial team. During hospital stay, patients were monitored for relapse of pain (primary endpoint), dietary intake, LOH (secondary endpoint), and 7 days postdischarge to record pain relapse rates. Results A total of 210 patients were included, 70 in each arm. On a per-protocol basis, there was no difference in pain relapse rates during refeeding between the 3 diet arms (P=0.80). Subjects initiated on a full solid diet consumed significantly more calories and fats on trial days 1 and 2 (P<0.001). A shorter LOH (median of –1.5 d) was observed among patients receiving a full solid diet without abdominal pain relapse (P=0.000). Conclusions Oral refeeding with a full solid diet in mild AP was well tolerated and resulted in a shorter LOH in patients without abdominal pain relapse.

Oral refeeding in patients with mild acute pancreatitis: prevalence and risk factors of relapsing abdominal pain.

Background and Aim:  In acute pancreatitis (AP), oral refeeding may stimulate pancreatic secretion, increasing the inflammation of the glandular tissue causing relapse of abdominal pain or even exacerbation of the disease. This study aimed to assess the prevalence and risk factors of abdominal pain relapse over oral refeeding in patients convalescing with AP as well as the impact of pain recurrence on the hospital stay.

Long‐term results with azathioprine therapy in patients with corticosteroid‐dependent Crohn’s disease: Open‐label prospective study

Background:  A substantial number of patients with Crohn’s disease (CD) become dependent on steroids after induction therapy. Treatment with azathioprine (AZA) may be beneficial in such patients. The present open‐label study evaluated the long‐term safety and efficacy of AZA in steroid‐dependent CD patients.

Idiopathic acute pancreatitis due to biliary sludge: prevention of relapses by endoscopic biliary sphincterotomy in high-risk patients.

“idiopathic” acute pancreatitis due to biliary sludge: prevention of relapses by endoscopic biliary sphincterotomy in high-risk patients

Fatal evolution of systemic lupus erythematosus associated with Crohn's disease

The authors describe the case of a young Brazilian woman who was treated of ileocolonic Crohns disease sparing rectum, as confirmed by colonoscopy and histopathological examination. After a 4-year course of sulfasalazine treatment, she presented with skin facial lesions in vespertilio, fever, arthralgias and high titers of anti-ANA and LE cells. A sulfasalazine-induced lupus syndrome was diagnosed, because after sulfasalazine withdrawal and a short course of prednisone, the clinical symptoms disappeared and the laboratory tests returned to normal. Mesalazine 3 g/day was started and the patient remained well for the next 3 years, when she was again admitted with fever, weakness, arthralgias, diplopy, strabismus and hypoaesthesia in both hands and feet, microhematuria, haematic casts, hypocomplementemia and high titers of autoimmune antibodies. A diagnosis of associated systemic lupus erythematosus was made. Although a pulsotherapy with methylprednisolone was started, no improvement was noticed. A cyclophosphamide trial was tried and again no positive results occurred. The patient evolved to severe clinical manifestations of general vasculitis affecting the central and peripheral nervous system and lungs, having a fatal evolution after 2 weeks. Although uncommon, the association of both disease may occur, and the authors call attention to this possibility, making a brief review of literature.

Effect of azathioprine or mesalazine therapy on incidence of re-hospitalization in sub-occlusive ileocecal Crohn’s disease patients

Background Although the cost of Crohn’s disease (CD) treatment differs considerably, hospitalization and surgery costs account for most of the total treatment cost. Decreasing hospitalization and surgery rates are pivotal issues in reducing health-care costs. Material/Methods We evaluated the effect of azathioprine (AZA) compared with mesalazine on incidence of re-hospitalizations due to all causes and for CD-related surgeries. In this controlled, randomized study, 72 subjects with sub-occlusive ileocecal CD were randomized for AZA (2–3 mg/kg per day) or mesalazine (3.2 g per day) therapy during a 3-year period. The primary end point was the re-hospitalization proportion due to all causes, as well as for surgical procedures during this period evaluated between the groups. Results On an intention-to-treat basis, the proportion of patients re-hospitalized within 36 months due to all causes was lower in patients treated with AZA compared to those on mesalazine (0.39 vs. 0.83, respectively; p=0.035). The AZA group had also significantly lower proportions of re-hospitalization for surgical intervention (0.25 vs. 0.56, respectively; p=0.011). The number of admissions (0.70 vs. 1.41, p=0.001) and the length of re-hospitalization (3.8 vs. 7.7 days; p=0.002) were both lower in AZA patients. Conclusions Patients with sub-occlusive ileocecal CD treated with AZA had lower re-hospitalization rates due to all causes and for surgical management of CD compared to those treated with mesalazine during a 3-year period. The long-term use of AZA in ileocecal CD patients recovering from a sub-occlusion episode can save healthcare costs.

Spontaneous bacterial peritonitis: How to deal with this life-threatening cirrhosis complication?

Spontaneous bacterial peritonitis (SBP) is one of the most common and life-threatening complications of cirrhosis. It occurs in 10% to 30% of patients admitted to hospital and recent studies tend to demonstrate that SBP incidence seems to be decreasing in its frequency. A bacterial overgrowth with translocation through the increased permeable small intestinal wall and impaired defense mechanisms is considered to be the main mechanism associated with its occurrence. The Gram-negative aerobic bacteria are the major responsible for SBP episodes and Gram-positive bacteria, mainly Staphylococcus aureus, are being considered an emergent agent causing SBP. The prompt diagnosis of SBP is the key factor for reduction observed in mortality rates in recent years. The clinical diagnosis of SBP is neither sensitive nor specific and the search for new practical and available tools for a rapid diagnosis of SBP is an important endpoint of current studies. Reagent strips were considered a promising and faster way of SBP diagnosis. The prompt use of empirical antibiotics, mostly cefotaxime, improves significantly the short-term prognosis of cirrhotic patients with SBP. The recurrence rate of SBP is high and antibiotic prophylaxis has been recommended in high-risk settings. Unfortunately, the long-term prognosis remains poor.

Autoimmune pancreatitis and hepatitis: an uncommon association

days and biological values returned to normal. Duodenal and gastric specimens taken 6 and 12 months after treatment initiation showed persistent infiltration by PAS-positive macrophages, but the intraabdominal lymphadenopathies had decreased in size and number on repeat CT. TMP-SMX was withdrawn after 1 yr. One month later, the patient presented with loss of appetite, weight loss, and biological signs of inflammation. TMP-SMX was resumed at the same dose as previously for 4 months, and the patient recovered rapidly. Symptoms and biological abnormalities again recurred on drug withdrawal. Despite further treatment with the same TMP-SMX regimen the symptoms worsened. Duodenal biopsies again showed infiltration by PAS-positive macrophages. Polymerase chain reaction (PCR) tests, using primers specific for the 16S rRNA gene of Tropheryma whippeliiwere positive on duodenal and gastric specimens but negative on peripheral blood. We concluded that the disease had relapsed and become resistant to TMP-SMX, and prescribed oral penicillin (Oracillin), 500,000 IU four times a day. The patient improved after 2 wk. After 1 yr of this therapy, the abdominal CT scan was normal, gastric biopsy specimens were normal, and duodenal biopsy specimens contained very few PASpositive macrophages. PCR tests of duodenal and gastric tissues and peripheral blood were negative. After 2 yr on the same treatment, the patient was still asymptomatic and PCR tests remained negative. Whipple’s disease is a systemic bacterial infection and the causative agent is Tropheryma whippelii , recently identified (1). Various empirical antibiotic regimens have been tested in this setting, such as tetracycline, TMP-SMX, cephalosporins, and penicillin. The optimal treatment period is poorly documented, but

Toxicidade da azatioprina na doença de Crohn: incidência, abordagem e evolução

1 yr is usually recommended. TMP-SMX has been found to induce complete clinical remission (2). We obtained a good initial response to TMPSMX therapy, followed by a relapse after drug discontinuation. The symptoms again responded to a second course of the same antibiotic, but a second relapse failed to respond to TMP-SMX. This, to our knowledge, is the first reported occurrence of acquired resistance to TMP-SMX. However, PCR has proved useful in diagnosing the disease and in monitoring bacterial eradication during antibiotic therapy (3). The positive amplification of duodenal and gastric samples during the third relapse indicated that the patient was still infected byTropheryma whippeliidespite TMP-SMX treatment, whereas the signal disappeared on oral penicillin. These negative PCR results on biopsy specimens were in keeping with the improvement in clinical manifestations and histological findings, which showed almost complete clearance of PAS-positive macrophage infiltration. This sequence of events suggests that repeated TMP-SMX treatment led to acquisition of resistance. PCR also has good predictive value for clinical relapse, with a negative predictive value of 100% when PCR results are negative (4). These findings raise the question of whether negative PCR results safely warrant treatment withdrawal. Long-term follow-up of treated patients is required to answer this question. The fact that the bacillus has been recently cultivated (5) provides hope for the possibility of testing antibiotic susceptibilities. Finally, this observation shows that oral penicillin is an effective, well tolerated alternative for chronic treatment of Whipple’s disease after failure of TMP-SMX.