Juan Martínez

Antibodies to carbonic anhydrase and IgG4 levels in idiopathic chronic pancreatitis: relevance for diagnosis of autoimmune pancreatitis

Background: Increased serum antibodies against carbonic anhydrase II (CA-II Ab) or IgG4 levels have been reported in cases of autoimmune chronic pancreatitis (ACP). Aim: To assess the relevance of serum CA-II Ab and IgG4 levels for the diagnosis of ACP in idiopathic CP (ICP) versus alcoholic CP and Sjögren’s syndrome (SS). Subjects: This was a multicentre study involving 227 subjects divided into four groups: ICP (n = 54), normal controls (n = 54, paired by age and sex with ICP patients), alcoholic CP (n = 86), and SS (n = 33). Methods: CA-II Ab was measured by ELISA and confirmed by western blotting. A score of easy clinical use with major clinical, morphological, and biochemical parameters for the diagnosis of ACP was applied. Results: The percentage of patients with increased serum CA-II Ab was higher in the ICP group (28%) than in controls (1.9%) and in patients with alcoholic CP (10.5%), but lower than in patients with SS (64%). The proportion with elevated IgG4 levels was higher in the ICP group (15%) compared with controls (1.9%) and SS (0%) but not significantly different from alcoholic CP (8%). Most ICP patients (7/8) with high IgG4 levels exhibited increased CA-II Ab and a compatible ACP score. A definitive diagnosis of ACP by histological analysis was associated with other autoimmune disorders, an increase in both serum IgG4 and CA-II Ab levels, and IgG4 positive plasma cells. Conclusions: The increase in serum IgG4 levels was strongly associated with elevated CA-II Ab levels, manifestations compatible with ACP, and lymphoplasmacytic infiltration when surgical specimens were available.

Factors Predicting Mortality in Severe Acute Pancreatitis

Acute pancreatitis (AP) is a common disorder in which ensuing serious complications may lead to a fatal outcome in patients. Background/Aims: To describe a large series of patients with severe AP (SAP) who were admitted to our hospital and to identify factors predicting mortality. Patients and Methods: In a retrospective study, all patients with SAP diagnosed between February 1996 and October 2000 according to the Atlanta criteria were studied. Results: Out of a total of 363 AP patients, 67 developed SAP. The mean age of the patients was 69; the commonest etiology was biliary; 55.2% developed necrosis; the commonest systemic complication was respiratory failure (44.7%), followed by acute renal failure (35.8%) and shock (20.9%). A total of 31.3% of the patients died. Factors significantly related to mortality were age, upper digestive tract bleeding, acute renal failure, respiratory failure and shock by univariate analysis. However, pseudocysts seemed to have a protective effect. By multivariate analysis, independent prognostic factors were age, acute renal failure and respiratory failure. Conclusions: Patients with SAP mainly died due to systemic complications, especially acute renal failure and respiratory failure. Necrosis (in the absence or presence of infection) was not correlated with increased mortality. A pseudocyst was found to be a protective factor, probably because the definition itself led to the selection of patients who had survived multiorgan failure.

Is Obesity a Risk Factor in Acute Pancreatitis? A Meta-Analysis

Background/Aims: Obesity has been associated with a worse prognosis in acute pancreatitis. According to some authors, obesity favours the development of local complications, while according to other reports obese patients presented more frequently systemic complications. Few studies find a relationship between obesity and mortality in acute pancreatitis. We conducted a meta-analysis of several reports that evaluate the relationship between obesity and the outcome of acute pancreatitis in order to assess its prognostic role in this disease. Methods: A MEDLINE search was conducted from 1965 to December 2002 with search terms including obesity, body mass index (BMI) and pancreatitis. A total of 12 reports were identified. Of these, only four studies included patients with mild and severe acute pancreatitis and measured obesity by BMI. The end points of the meta-analysis were the severity of acute pancreatitis, local complications, systemic complications and mortality. Obesity was defined when BMI was ≧30 kg/m2. Pooled odds ratio (OR) and confidence intervals (CI) were calculated according to the Mantel-Haenszel method, and heterogeneity was assessed by the multiplicative inverse variance method. Results: A total of 607 patients were evaluated. There was no heterogeneity for the variables severity, systemic complications, local complications and mortality among the included studies. Severe AP was significantly more frequent in obese patients (OR 2.6, 95% CI 1.5–4.6). Furthermore, those patients developed significantly more systemic (OR 2.0, 95% CI 1.1–4.6) and local complications (OR 4.3, 95% CI 2.4–7.9). Mortality in obese patients was only slightly higher (OR 1.3, 95% CI 0.5–3.6). Conclusion: Obesity is a prognostic factor favouring the development of systemic and local complications in this disease. Therefore, it should be used routinely as part of the initial assessment of the severity of a case of acute pancreatitis.

Obesity : A prognostic factor of severity in acute pancreatitis

This study was conducted to assess the prognostic value of obesity in acute pancreatitis and to determine the role played by obesity-associated diseases in the course of the disease. We prospectively studied 49 patients with acute pancreatitis who were divided into three groups according to their body mass index (BMI). There were 22 patients in group I (BMI < or = 25 kg/m2, normal or low weight); 15 in group II (BMI >25 and < or = 29 kg/m2, overweight); and 12 in group III (BMI >29 kg/m2, obese). Other anthropometric parameters also were measured. The severity of pancreatitis was assessed according to the Atlanta classification system. Systemic complications were significantly more common among obese than nonobese patients (p < 0.05). Patients with severe pancreatitis had a higher body-fat percentage, measured by the subscapular skin-fold thickness, and a larger abdominal circumference than patients with mild pancreatitis. Although hypertensive or diabetic patients developed more systemic complications, the multivariate analysis demonstrated that the presence of these underlying diseases did not modify the prognostic role of obesity in acute pancreatitis. We conclude that obesity is a prognostic factor of outcome in acute pancreatitis. Obesity-associated diseases do not vary the prognostic value of obesity. It seems that truncal adiposity is the kind of obesity related to worse outcome of acute pancreatitis.

Obesity and Fat Distribution Imply a Greater Systemic Inflammatory Response and a Worse Prognosis in Acute Pancreatitis

Background and Aims: Acute pancreatitis (AP) is a systemic inflammatory disease. It is already known that obesity and central fat distribution are related to the severity of AP, but the intimate mechanism of this relationship remains unknown. Obesity and central fat distribution are associated with an inflammatory state that could amplify the systemic inflammatory response (SIR) in AP. The aim of this study was to investigate how obesity and body fat distribution correlate with the SIR and severity of AP. Methods: 85 consecutive patients with AP were studied. Body mass index, body fat distribution and previous comorbidity were obtained at admission. The SIR was assessed by the serum levels of interleukin (IL)-1β, IL-1ra, IL-6, IL-8, IL-10, IL-12p70, tumor necrosis factor-α (TNF-α) and C-reactive protein. Serum concentrations of the previously mentioned cytokines were also determined in a control group of 40 healthy volunteers. Results: 63 patients (74%) had mild AP and 22 patients (26%) had severe AP. All the cytokines except IL-12p70 and TNF-α were increased in the AP group in comparison with the control group. The SIR was significantly increased in patients with severe AP. Obese patients and patients with central fat distribution had significantly more comorbidity, a higher proportion of severe AP and more intense SIR. Patients with comorbidity had a significantly higher proportion of severe AP and more SIR. Conclusion: The severity of AP in obese patients and in patients with central fat distribution seems to be related to the comorbidity and the amplification of SIR.

Deep sedation with propofol does not precipitate hepatic encephalopathy during elective upper endoscopy

BACKGROUND The risk of hepatic encephalopathy (HE) precipitated by propofol has not been established. OBJECTIVE To know whether the use of propofol for endoscopy in patients with cirrhosis induces minimal or overt HE. DESIGN A cohort study. SETTING A tertiary-referral university hospital endoscopy unit. PATIENTS Patients with cirrhosis who received an endoscopy with propofol sedation. We excluded patients with clinical HE. A group of patients without liver disease was included to compare the incidence of adverse effects. INTERVENTIONS Minimal HE (MHE) was diagnosed by using the psychometric hepatic encephalopathy score (PHES) battery of psychometric tests. Cognitive status before and 1 hour after the endoscopy was evaluated by measuring the critical flicker frequency (CFF). MAIN OUTCOME MEASUREMENTS Overt and minimal HE. RESULTS Twenty patients with cirrhosis and 20 patients without cirrhosis were included. There were no differences between groups in the incidence of adverse effects. Thirteen patients (65%) had MHE before the endoscopy. No patient developed overt HE after sedation. We did not observe differences in CFF before and after sedation in patients without MHE: median (25th-75th percentile), 40.8 Hz (37.1-46.0 Hz) versus 41.1 Hz (36.0-44.3 Hz), P = .8). None of the patients who were without MHE showed a decrease in the CFF under the cutoff of 39 Hz after sedation. There were not significant changes in CFF before and after propofol sedation in patients previously diagnosed of MHE: median (25th-75th percentile), 40.6 Hz (36.8-49.1 Hz) versus 42.7 Hz (36.8-52.4 Hz), P = .08. LIMITATION A small number of patients were included in the study. CONCLUSIONS The use of propofol in the sedation of patients with cirrhosis during endoscopic procedures does not precipitate minimal or overt HE.

A study of intestinal permeability in relation to the inflammatory response and plasma Endocab IgM levels in Patients with acute pancreatitis

Background: There is scarce information regarding intestinal permeability (IP) in patients with acute pancreatitis (AP) and its relationship with systemic inflammatory response and bacterial translocation (BT). Aims: To study IP in patients with mild and severe forms of AP as compared with controls and the presumed correlations between IP, the inflammatory response, and endotoxin. Patients and methods: Sixty-eight patients with AP and 13 healthy controls were included. IP was assessed by means of the lactulose/mannitol (L/M) test, at admission (LMR1), and at the 15th day (LMR2). The presence of endotoxin was assessed by means of endotoxin-core antibodies type IgM (EndoCab IgM), at admission and 15 days later in patients with severe AP. Plasma levels of interleukins 6, 8, 10, and tumor necrosis factor α were tested within the first 72 hours from the onset of pain. Results: Both LMR1 and LMR2 were significantly higher in patients than in controls, and in patients with severe versus mild forms of AP. Plasma levels of Endocab IgM increased significantly in patients with severe AP. Basal plasma levels of pro- and anti-inflammatory cytokines were significantly higher in patients with severe AP. A significant correlation was found between LMR2 and Endocab IgM levels in patients with severe AP (r = 0.73, P = 0.02). Conclusions: Patients with AP show an increased IP when compared with controls, being more relevant and persistent in severe cases. This seems related to an increase of endotoxemia late in the course of the disease, but not with an exacerbation of the systemic immune response.

The Spanish Pancreatic Club's recommendations for the diagnosis and treatment of chronic pancreatitis: part 2 (treatment).

Chronic pancreatitis (CP) is a complex disease with a wide range of clinical manifestations. This range comprises from asymptomatic patients to patients with disabling symptoms or complications. The management of CP is frequently different between geographic areas and even medical centers. This is due to the paucity of high quality studies and clinical practice guidelines regarding its diagnosis and treatment. The aim of the Spanish Pancreatic Club was to give current evidence-based recommendations for the management of CP. Two coordinators chose a multidisciplinary panel of 24 experts on this disease. These experts were selected according to clinical and research experience in CP. A list of questions was made and two experts reviewed each question. A draft was later produced and discussed with the entire panel of experts in a face-to-face meeting. The level of evidence was based on the ratings given by the Oxford Centre for Evidence-Based Medicine. In the second part of the consensus, recommendations were given regarding the management of pain, pseudocysts, duodenal and biliary stenosis, pancreatic fistula and ascites, left portal hypertension, diabetes mellitus, exocrine pancreatic insufficiency, and nutritional support in CP.

Effects of pretreatment with intravenous flecainide on efficacy of external cardioversion of persistent atrial fibrillation.

Electrical cardioversion is the most effective and safe method to restore sinus rhythm in patients with persistent AF. However, at least 25% of electrical cardioversions are unsuccessful. The aim of the present study was to evaluate, in a prospective, randomized and double‐blind study, the efficacy of a pretreatment with intravenous flecainide in patients who underwent electrical cardioversion. Fifty‐four consecutive patients with persistent AF, mean arrhythmia duration 8 (mean 3–18) weeks, were randomized in two groups. In the first group (n = 26), patients received flecainide (2 mg/kg as a 30‐minute IV infusion) before electrical cardioversion. In the second group (n = 28), 100 mL IV infusion of 5% glucose was administered 30 minutes before electrical cardioversion. The study evaluated the (1) acute efficacy of electrical cardioversion, (2) mean and maximal energy required, (3) mean number of shocks needed, and (4) incidence of complications. The two groups were similar in terms of age, sex, mean AF duration, left ventricular systolic function, atrial dimension, and cardiovascular risk factors. Seventy‐seven percent of patients recovered sinus rhythm with electrical cardioversion. No statistical difference was noted between the two groups: flecainide 19/26 (73%) versus placebo 23/28 (82%). No significant differences were found concerning mean or maximal energy and number of shocks required. No major complications were observed. After a 30‐day follow‐up, 54% of patients maintained sinus rhythm with no difference between the two groups. Pretreatment with intravenous flecainide before electrical cardioversion is not useful in reducing technical failure of cardioversion, however, flecainide does not diminish the effectiveness of electrical cardioversion. (PACE 2004; 27:368–372)

The Spanish Pancreatic Club recommendations for the diagnosis and treatment of chronic pancreatitis: Part 1 (diagnosis)

Chronic pancreatitis (CP) is a relatively uncommon, complex and heterogeneous disease. The absence of a gold standard applicable to the initial phases of CP makes its early diagnosis difficult. Some of its complications, particularly chronic pain, can be difficult to manage. There is much variability in the diagnosis and treatment of CP and its complications amongst centers and professionals. The Spanish Pancreatic Club has developed a consensus on the management of CP. Two coordinators chose a multidisciplinary panel of 24 experts on this disease. A list of questions was drafted, and two experts reviewed each question. Then, a draft was produced and shared with the entire panel of experts and discussed in a face-to-face meeting. This first part of the consensus addresses the diagnosis of CP and its complications.