Individualized PEEP setting in subjects with ARDS: a randomized controlled pilot study.

BACKGROUND: Low-tidal-volume ventilation may be associated with repetitive opening and closing of terminal airways. The use of PEEP is intended to keep the alveoli open. No method of adjusting the optimal PEEP has shown to be superior or to improve clinical outcomes. We conducted a pilot study to evaluate the effect of setting an individualized level of PEEP at the highest compliance on oxygenation, multiple-organ-dysfunction, and survival in subjects with ARDS. METHODS: Subjects with ARDS ventilated with low tidal volumes and limitation of airway pressure to 30 cm H2O were randomized to either a compliance-guided PEEP group or an FIO2-guided group. RESULTS: Of the 159 patients with ARDS admitted during the study period, 70 met the inclusion criteria. Subjects in the compliance-guided group showed nonsignificant improvements in PaO2/FIO2 during the first 14 days, and in 28-day mortality (20.6% vs. 38.9%, P = .12). Multiple-organ-dysfunction-free days (median 6 vs 20.5 d, P = .02), respiratory-failure-free days (median 7.5 vs 14.5 d, P = .03), and hemodynamic-failure-free days (median 16 vs 22 d, P = .04) at 28 days were significantly lower in subjects with compliance-guided setting of PEEP. CONCLUSIONS: In ARDS subjects, protective mechanical ventilation with PEEP application according to the highest compliance was associated with less organ dysfunction and a strong nonsignificant trend toward lower mortality. ClinicalTrials.gov Number NCT01119872.

Diagnostic accuracy and therapeutic impact of endoscopic ultrasonography in patients with intermediate suspicion of choledocholithiasis and absence of findings in magnetic resonance cholangiography.

BACKGROUND: endoscopic ultrasonography (EUS) and magnetic resonance cholangiography (MRC) are the elective tests in the diagnosis of choledocholithiasis. MRC is best accepted by patients, but its sensitivity might decrease in the evaluation of microlithiasis. AIM: to evaluate the diagnostic accuracy and therapeutic impact of EUS in a prospective cohort of patients with intermediate suspicion of choledocolithiasis and no findings in MRC (normal MRC). MATERIAL AND METHODS: during a period of 24 months, all the patients with clinical intermediate suspicion of choledocholithiasis and normal MRC were included. Sensitivity, specificity, diagnostic accuracy, positive predictive value (PPV) and negative predictive value (NPV) of MRC and EUS were compared, and so their impact in the management of these patients. RESULTS: seventy six patients were evaluated (lithiasis in 30% of them). Sensitivity and diagnostic accuracy of EUS (100%, 92%) were significantly higher than MRC values (0%, 70%) (p < 0.05). EUS findings (suspicion of choledocholithiasis) favored a significant change in therapeutic attitude (therapeutic ERCP was performed) in 38% of the patients (in which MRC had ruled out the presence of choledocholithiasis, and so, ERCP had not been performed) (p < 0.05). CONCLUSIONS: EUS allows the diagnosis of lithiasis in approximately 1/3 of patients with intermediate suspicion of choledocholithiasis and normal MRC. EUS findings involve a significant change in the management of these patients; this supports the use of EUS in clinical practice.

Optimized protocol for diagnosis of acute ileitis.

BACKGROUND & AIMS: Suspected acute ileitis (AI) is a poorly defined clinical condition with multiple causes; its diagnostic protocol has not been standardized properly. We performed a prospective evaluation of the incidence and causes of AI to create a standard protocol for diagnosis. METHODS: The definition of AI included abdominal pain, diarrhea, fever, and at least 1 confirmatory imaging method (abdominal computed tomography scan or ultrasound) showing pathologic changes in the terminal ileum that indicated ileal inflammation. We studied all patients with a presumptive diagnosis of AI seen in the Emergency Room at the Ramón y Cajal Hospital in Madrid, from March 2005 to May 2007, according to a pre-established protocol. Sixty-six patients with primary AI were followed up for at least 6 months. RESULTS: An infectious cause was found in 33.3% of cases; the most frequently detected microorganism was Yersinia spp. A gynecologic condition was identified in 9.1% of cases initially diagnosed as AI, representing 13.95% of the cases among female patients. Crohn's disease was identified in 12.1% of patients. The diagnostic protocol led to negative results in 33.4% of the patients; 6.1% of patients did not complete the study. The initial diagnosis did not change among any of the patients during the follow-up period. CONCLUSIONS: This protocol led to a definitive diagnosis of AI in more than 60% of potential cases. The most common cause was acute infection. About 10% of cases were of gynecologic origin and about 12% of patients presented with Crohn's disease.

Open-label infliximab therapy in Crohn's disease: a long-term multicenter study of efficacy, safety and predictors of response.

BACKGROUND: Efficacy of infliximab in Crohn's disease (CD) showed by randomized controlled trials must be confirmed in clinical practice. We aimed to evaluate efficacy and safety of infliximab in CD patients of the Madrid area, looking for clinical predictors of response. METHODS: Multicenter retrospective survey of all CD patients treated with infliximab in 8 University hospitals of the Madrid area (Spain) with a minimum follow up of 14 wks. RESULTS: 169 patients included (48%males, mean age 39 +/- 12 yrs). 64% of them had perianal disease. 82% were under immunosuppressants. 1,355 infliximab infusions administered (mean 8, range 1-30). 90% response rate and 48% remission rate were obtained with induction therapy. 73% followed maintenance treatment, and 78% of them maintained or improved the response after a mean follow up of 28 months (range 3.5-86). 24 patients lost response during the follow up, after a mean of 41 wks (range 6-248). Only the prescription of maintenance therapy was predictive factor for favourable response (p < 0.01). 17 infusion reactions were reported (10% of the patients, 1.2% of the infusions; only one case was severe) and were the cause of treatment withdrawal in 7 patients. Co-treatment with immunosuppressive drugs and maintenance infliximab therapy were protective factors for infusion reactions (p < 0.05). Other adverse events occurred in 26% of the patients, and were cause of treatment withdrawal in 7 patients. CONCLUSIONS: Infliximab is effective and safe for CD management but concomitant immunosuppressive drugs and maintenance treatment should be prescribed to obtain the best outcome. That confirms in a real life clinical setting the favourable results obtained in randomized clinical trials.

Severe everolimus-associated pneumonitis in a renal transplant recipient.

Inhibitors of mTOR (mammalian target of rapamycin) are immunosuppressants with less nephrotoxic potential than calcineurin inhibitors and antiproliferative effects, which are advantageous in the case of malignancy. However, a series of adverse events has been reported with the first-generation mTOR inhibitor sirolimus that includes hypersensitivity-like interstitial pneumonitis. To our knowledge, only one case of a pneumonitis associated with everolimus in a heart transplant patient has been reported, and it was related to elevated trough blood levels. We report herein the first case of a kidney graft recipient who developed everolimus-associated pneumonitis with normal trough blood levels that was completely reversed after drug withdrawal.

Usefulness of penicillamine-stimulated urinary copper excretion in the diagnosis of adult Wilson's disease.

OBJECTIVE: Diagnosis of Wilson's disease (WD) is reliant on liver biopsy (LB) and measurement of hepatic copper. The aim of this study was to determine the usefulness of penicillamine-stimulated urinary copper excretion (PS-UCE), a non-invasive diagnostic test, for the diagnosis of WD in adults. MATERIAL AND METHODS: In this prospective study of patients with suspected WD, total serum copper, ceruloplasmin, basal 24-h UCE and PS-UCE levels were measured. LB with copper determination was performed in those patients with persistent hypertransaminasemia and low ceruloplasmin or basal UCE > 40 microg/24 h. Diagnosis was established if the ceruloplasmin level was found to be < 20 mg/dl and hepatic copper > 250 microg/g. Results. A total of 115 patients were studied; LB was performed in 43, and WD was diagnosed in 6 (13.9%). Significant differences between WD and non-WD patients were found for basal UCE (WD: median 134.3 microg/24 h versus non-WD: median 19.0 microg/24 h (p < 0.05)) and PS-UCE (WD: median 1284.0 microg/24 h versus non-WD: median 776.0 microg/24 h; p < 0.01). In the ROC (receiver-operated curve) analysis, PS-UCE was the best discriminant between WD and non-WD (area under the curve (AUC) = 0.911, best cut-off point 1057 microg/24 h, 100% sensitivity, 82.3% specificity). CONCLUSIONS: PS-UCE is probably a useful non-invasive test in the diagnosis of WD, improving the selection of patients for diagnostic liver biopsy. Patients with PS-UCE under 1057 microg/24 h only rarely will suffer from WD and are unlikely to benefit from LB.

[Acute hepatitis E in Madrid: description of 18 cases]. / Hepatitis aguda E en Madrid: descripción de 18 casos.

INTRODUCTION: Hepatitis E virus (HEV) is the main cause of non-A non-B enterically transmitted hepatitis in underdeveloped countries but is rare in industrialized areas. However, in the last few years, several sporadic autochthonous hepatitis E cases have been reported in Europe and no risk factors, such as visiting to endemic areas, could be found in these patients. OBJECTIVE AND PATIENTS: Twelve patients with sporadic autochthonous hepatitis E (no risk factors such as traveling to endemic areas) and six imported cases (travel to Nepal, Santo Domingo, China, Brazil and Ecuador) were studied between June 1999 and December 2005. RESULTS: HEV infection was diagnosed in patients with symptoms of acute hepatitis and the presence of IgG and IgM antibodies in serum with no other markers of hepatitis. HEV infection is probably overlooked in industrialized countries. CONCLUSIONS: This diagnosis should be suspected in patients with acute hepatitis and anti-HEV antibodies in serum without known risk factors such as traveling to endemic areas.

Circulatory function and hepatorenal syndrome in cirrhosis.

The pathogenic mechanism of hepatorenal syndrome is not well established. We investigated the circulatory function in cirrhosis before and after the development of hepatorenal syndrome. Systemic and hepatic hemodynamics and the activity of endogenous vasoactive systems were measured in 66 patients who had cirrhosis with tense ascites and normal serum creatinine levels; measurements were repeated at follow-up in 27 cases in whom hepatorenal syndrome had developed. At baseline, mean arterial pressure and cardiac output were significantly higher, and hepatic venous pressure gradient, plasma renin activity, and norepinephrine concentration were significantly lower in patients who did not develop hepatorenal syndrome compared with those presenting with this complication. Peripheral vascular resistance was decreased to the same extent in the two groups. Plasma renin activity and cardiac output were the only independent predictors of hepatorenal syndrome. Hepatorenal syndrome occurred in the setting of a significant reduction in mean arterial pressure (83 +/- 9 to 75 +/- 7 mmHg; P < .001), cardiac output (6.0 +/- 1.2 to 5.4 +/- 1.5 L/min; P < .01), and wedged pulmonary pressure (9.2 +/- 2.6 to 7.5 +/- 2.6 mmHg; P < .001) and an increase in plasma renin activity (9.9 +/- 5.2 to 17.5 +/- 11.4 ng/mL . hr; P < .001), norepinephrine concentration (571 +/- 241 to 965 +/- 502 pg/mL; P < .001), and hepatic venous pressure gradient. No changes were observed in peripheral vascular resistance. In conclusion, these data indicate that hepatorenal syndrome is the result of a decrease in cardiac output in the setting of a severe arterial vasodilation.