Risk stratification in acute variceal bleeding: Far from an ideal score.

OBJECTIVES: Acute variceal bleeding (AVB) results from rupture of esophageal or gastric varices. It is a life-threatening complication of portal hypertension. Nevertheless, it remains unclear how to predict adverse outcomes and identify high-risk patients. In variceal hemorrhage, high Child-Turcotte-Pugh (Child) and Model for End-stage Liver Disease (MELD) scores are associated with a worse prognosis. The Rockall system (Rockall), Glasgow-Blatchford (Blatchford), and AIMS65 scores have been validated for risk stratification for nonvariceal upper gastrointestinal bleeding; however, their use is controversial in AVB. The aim of this study was to compare the performance of Child, MELD, Rockall, Blatchford, and AIMS65 scores in risk stratification for rebleeding and/or mortality associated with AVB. METHODS: This retrospective study was conducted at a tertiary care hospital over 42 months. The outcomes were 6-week rebleeding and mortality. The AUROC was calculated for each score (1-0.9, 0.9-0.8, and 0.8-0.7, indicating excellent, good, and acceptable predictive power, respectively). RESULTS: In total, 222 patients were included. Six-week rebleeding and mortality rates were 14% and 18.5%, respectively. No score was useful for discriminating patients at a higher risk of rebleeding. The AUROCs were 0.59, 0.57, 0.61, 0.63, and 0.56 for Rockall, Blatchford, AIMS65, Child, and MELD scores, respectively. Prediction of 6-week mortality based on Rockall (AUROC 0.65), Blatchford (AUROC=0.60), and AIMS65 (AUROC=0.67) scores were also not considered acceptable. The AUROCs for predicting mortality were acceptable for Child and MELD scores (0.72 and 0.74, respectively). CONCLUSION: Rockall, Blatchford, and AIMS65 scores are not useful for predicting 6-week rebleeding or mortality in patients with AVB. Child and MELD scores can identify patients at higher risk for 6-week mortality but not for 6-week rebleeding.

Anti-TNF therapy and immunogenicity in inflammatory bowel diseases: a translational approach.

Inflammatory bowel diseases are chronic illnesses that involve intestinal inflammation and are usually diagnosed as Crohn's disease or ulcerative colitis. As these diseases do not have a cure, the goal of treatment is to induce and maintain remission. Monoclonal antibodies have been recognized as the most advanced therapy to avoid complications and reduce the need for surgical approaches. However, although their effectiveness has been proven by several studies, they can trigger the immune system, induce the occurrence of immunogenicity, which may lead to the loss of response and treatment failure. The purpose of this review is to determine what are the main mechanisms involved in IBD; to assess the recommended treatments; to explore the mechanisms of immunogenicity. We also try to explain the detection and describe the existing advances that make possible the clinical application of these approaches.

Assessment of disease activity in inflammatory bowel diseases: Non-invasive biomarkers and endoscopic scores.

Inflammatory bowel diseases (IBD) comprise two major forms: Crohn's disease and ulcerative colitis. The diagnosis of IBD is based on clinical symptoms combined with results found in endoscopic and radiological examinations. In addition, the discovery of biomarkers has significantly improved the diagnosis and management of IBD. Several potential genetic, serological, fecal, microbial, histological and immunological biomarkers have been proposed for IBD, and they have been evaluated for clinical routine and clinical trials. Ileocolonoscopy, especially with biopsy collection, has been considered the standard method to diagnose IBD and to assess clinical activity of the disease, but it is limited to the colon and terminal ileum and is considered invasive. For this reason, non-invasive biomarkers are necessary for this type of chronic inflammatory disease, which affects mostly young individuals, as they are expected to have a long follow-up.

Investigation of autonomic function and orocecal transit time in patients with nonalcoholic cirrhosis and the potential influence of these factors on disease outcome.

BACKGROUND: The presence of autonomic dysfunction in nonalcoholic cirrhosis and its influence on intestinal transit and disease outcome still need clarification. GOALS: To investigate the function of the autonomic nervous system in patients with nonalcoholic cirrhosis and the possible associations among autonomic dysfunction, severity of liver disease, disturbed intestinal transit, and the development of complications during follow-up. STUDY: Measurements of heart rate variability obtained by analysis of 24-hour ambulatory electrocardiographic recordings to assess autonomic function and lactulose breath hydrogen test to determine orocecal transit time were performed in 32 patients with nonalcoholic cirrhosis divided into Child A and B. RESULTS: Child B patients showed significantly lower values (P<0.05) of those parameters reflecting parasympathetic (high frequency, log-transformed high frequency, pNN50) and sympathetic function (low frequency, log-transformed low frequency) in comparison with controls and Child A patients. Orocecal transit time values were significantly (P=0.02) higher in Child B patients than in controls, but no relationship was found between delayed orocecal transit time and autonomic dysfunction. During follow-up, 42% of Child B patients developed encephalopathy. This complication was significantly associated with autonomic dysfunction. In addition, in the 4 patients who died the parameters reflecting parasympathetic function were significantly reduced in comparison with those of survivors. CONCLUSIONS: Autonomic dysfunction and delayed intestinal transit are related to the severity of disease in nonalcoholic cirrhosis. Autonomic dysfunction seems to predispose cirrhotic patients to the development of encephalopathy and may be associated with a poor prognosis of these patients.

Irritable bowel syndrome: associations between FODMAPS intake, problematic foods, adiposity, and gastrointestinal symptoms.

This study investigated the association between fermentable oligo-di-mono-saccharides and polyols (FODMAPs) intake, problematic foods, body adiposity, and gastrointestinal symptoms in 44 women with irritable bowel syndrome (IBS). Around 84% reported to have excluded some food from their diet. Adiposity was not associated with the frequency of gastrointestinal symptoms and IBS severity. Controlling for BMI, there were significant correlations between number of problematic foods versus waist circumference (r = 0.306; p = 0.049) and protein intake (r = -0.378; p = 0.014). The IBS severity correlated to the carbohydrate intake (r = -0.320; p = 0.039). Patients with diarrhea demonstrated statistical tendency to restrict the intake of fat (p = 0.058), free fructose (p = 0.07), and oligosaccharides (p = 0.051). Patients with mucus in the stool had higher lactose intake (p = 0.025). The number of food considered problematic was higher for patients who reported stomach burning (p = 0.0001). Associations among adiposity, gastrointestinal symptoms, problematic food, and FODMAPs were identified and reaffirm the role of individualized nutritional treatment in the management of IBS.

Risk stratification in acute variceal bleeding: Far from an ideal score

OBJECTIVES: Acute variceal bleeding (AVB) results from rupture of esophageal or gastric varices. It is a life-threatening complication of portal hypertension. Nevertheless, it remains unclear how to predict adverse outcomes and identify high-risk patients. In variceal hemorrhage, high Child-Turcotte-Pugh (Child) and Model for End-stage Liver Disease (MELD) scores are associated with a worse prognosis. The Rockall system (Rockall), Glasgow-Blatchford (Blatchford), and AIMS65 scores have been validated for risk stratification for nonvariceal upper gastrointestinal bleeding; however, their use is controversial in AVB. The aim of this study was to compare the performance of Child, MELD, Rockall, Blatchford, and AIMS65 scores in risk stratification for rebleeding and/or mortality associated with AVB. METHODS: This retrospective study was conducted at a tertiary care hospital over 42 months. The outcomes were 6-week rebleeding and mortality. The AUROC was calculated for each score (1-0.9, 0.9-0.8, and 0.8-0.7, indicating excellent, good, and acceptable predictive power, respectively). RESULTS: In total, 222 patients were included. Six-week rebleeding and mortality rates were 14% and 18.5%, respectively. No score was useful for discriminating patients at a higher risk of rebleeding. The AUROCs were 0.59, 0.57, 0.61, 0.63, and 0.56 for Rockall, Blatchford, AIMS65, Child, and MELD scores, respectively. Prediction of 6-week mortality based on Rockall (AUROC 0.65), Blatchford (AUROC=0.60), and AIMS65 (AUROC=0.67) scores were also not considered acceptable. The AUROCs for predicting mortality were acceptable for Child and MELD scores (0.72 and 0.74, respectively). CONCLUSION: Rockall, Blatchford, and AIMS65 scores are not useful for predicting 6-week rebleeding or mortality in patients with AVB. Child and MELD scores can identify patients at higher risk for 6-week mortality but not for 6-week rebleeding.

Resistance Surveillance in Candida albicans: A Five-Year Antifungal Susceptibility Evaluation in a Brazilian University Hospital.

Candida albicans caused 44% of the overall candidemia episodes from 2006 to 2010 in our university tertiary care hospital. As different antifungal agents are used in therapy and also immunocompromised patients receive fluconazole prophylaxis in our institution, this study aimed to perform an antifungal susceptibility surveillance with the C.albicans bloodstream isolates and to characterize the fluconazole resistance in 2 non-blood C.albicans isolates by sequencing ERG11 gene. The study included 147 C. albicans bloodstream samples and 2 fluconazole resistant isolates: one from oral cavity (LIF 12560 fluconazole MIC: 8µg/mL) and one from esophageal cavity (LIF-E10 fluconazole MIC: 64µg/mL) of two different patients previously treated with oral fluconazole. The in vitro antifungal susceptibility to amphotericin B (AMB), 5-flucytosine (5FC), fluconazole (FLC), itraconazole (ITC), voriconazole (VRC), caspofungin (CASP) was performed by broth microdilution methodology recommended by the Clinical and Laboratory Standards Institute documents (M27-A3 and M27-S4, CLSI). All blood isolates were classified as susceptible according to CLSI guidelines for all evaluated antifungal agents (MIC range: 0,125-1.00 µg/mL for AMB, ≤0.125-1.00 µg/mL for 5FC, ≤0.125-0.5 µg/mL for FLC, ≤0.015-0.125 µg/mL for ITC, ≤0.015-0.06 µg/mL for VRC and ≤0.015-0.125 µg/mL for CASP). In this study, we also amplified and sequenced the ERG11 gene of LIF 12560 and LIF-E10 C.albicans isolates. Six mutations encoding distinct amino acid substitutions were found (E116D, T128K, E266D, A298V, G448V and G464S) and these mutations were previously described as associated with fluconazole resistance. Despite the large consumption of antifungals in our institution, resistant blood isolates were not found over the trial period. Further studies should be conducted, but it may be that the very prolonged direct contact with the oral antifungal agent administered to the patient from which was isolated LIF E-10, may have contributed to the development of resistance.

Dyspeptic symptoms in patients with type 1 diabetes: endoscopic findings, Helicobacter pylori infection, and associations with metabolic control, mood disorders and nutritional factors.

OBJECTIVES: To evaluate, in a group of patients with long-standing type 1 diabetes (DM1), an association of dyspepsia symptoms with: changes in the gastroduodenal mucosa, infection by Helicobacter pylori, glycemic control, and psychological and nutritional factors. SUBJECTS AND METHODS: A total of 32 patient with DM1 were studied (age: 38 ± 9 years; females: 25; diabetes duration: 22 ± 5 years). All patients answered a standardized questionnaire for the evaluation of gastrointestinal symptoms and underwent upper gastrointestinal endoscopy, with gastric biopsies for the evaluation of Helicobacter pylori infection. The presence of anxiety and depression was evaluated by the HAD scale. Nutritional parameters were BMI, arm and waist circumference, skinfold measurement, and body fat percentage. RESULTS: Upper endoscopy detected lesions in the gastric mucosa in 34.4% of the patients, with similar frequency in those with (n = 21) and without dyspepsia (n = 11). The patients with dyspepsia complaints showed greater frequency of depression (60% vs. 0%; p = 0.001), higher values for HbA1c (9.6 ± 1.7 vs. 8.2 ± 1.3%; p = 0.01) and lower values for BMI (24.3 ± 4.1 vs. 27.2 ± 2.6 kg/m2; p = 0.02), body fat percentage (26.6 ± 6.2 vs. 30.8 ± 7.7%; p = 0.04), and waist circumference (78.7 ± 8 vs. 85.8 ± 8.1 cm; p = 0.02). No association was found between the symptoms and the presence of Helicobacter pylori. CONCLUSIONS: Dyspepsia symptoms in patients with long-standing DM1 were associated with glycemic control and depression, and they seem to negatively influence the nutritional status of these patients.

Gastrointestinal involvement in lipoid proteinosis: a ten-year follow-up of a brazilian female patient.

Lipoid proteinosis is a rare autosomal recessive disease characterized by the deposition of hyaline material in the skin and internal organs. The main clinical features are hoarseness and typical skin lesions. In this report we describe the endoscopic and radiologic findings in a Brazilian female patient presenting extensive gastrointestinal involvement and the evolution of the detected lesions in ten years of follow-up. Initial upper endoscopy and colonoscopy showed a similar pattern of multiple yellowish nodules throughout the esophagus, stomach, duodenum, and colons. Histological analysis confirmed the diagnosis of lipoid proteinosis. In addition, small bowel follow through demonstrated numerous well defined, round, small filling defects throughout the jejunum. Ten years later, the esophageal lesions remained the same, but none of the previous alterations were detected in the stomach, duodenum, and colons. In conclusion, lipoid proteinosis may affect all gastrointestinal organs with the same pattern of macroscopic and microscopic lesions. Some lesions may regress with increasing age.

Giardia infection: protein-losing enteropathy in an adult with immunodeficiency.

The case of a 52-year-old woman with a past history of thymoma resection who presented with chronic diarrhea and generalized edema is the focal point of this article. A diagnosis of Giardia lamblia infection was established, which was complicated by protein-losing enteropathy and severely low serum protein level in a patient with no urinary protein loss and normal liver function. After anti-helmintic treatment, there was recovery from hypoalbuminemia, though immunoglobulins persisted at low serum levels leading to the hypothesis of an immune system disorder. Good's syndrome is a rare cause of immunodeficiency characterized by the association of hypogammaglobulinemia and thymoma. This primary immune disorder may be complicated by severe infectious diarrhea secondary to disabled humoral and cellular immune response. This is the first description in the literature of an adult patient with an immunodeficiency syndrome who presented with protein-losing enteropathy secondary to giardiasis.

Dyspeptic symptoms in patients with type 1 diabetes: endoscopic findings, Helicobacter pylori infection, and associations with metabolic control, mood disorders and nutritional factors

Objectives To evaluate, in a group of patients with long-standing type 1 diabetes (DM1), an association of dyspepsia symptoms with: changes in the gastroduodenal mucosa, infection by Helicobacter pylori, glycemic control, and psychological and nutritional factors. Subjects and methods A total of 32 patient with DM1 were studied (age: 38 ± 9 years; females: 25; diabetes duration: 22 ± 5 years). All patients answered a standardized questionnaire for the evaluation of gastrointestinal symptoms and underwent upper gastrointestinal endoscopy, with gastric biopsies for the evaluation of Helicobacter pylori infection. The presence of anxiety and depression was evaluated by the HAD scale. Nutritional parameters were BMI, arm and waist circumference, skinfold measurement, and body fat percentage. Results Upper endoscopy detected lesions in the gastric mucosa in 34.4% of the patients, with similar frequency in those with (n = 21) and without dyspepsia (n = 11). The patients with dyspepsia complaints showed greater frequency of depression (60% vs. 0%; p = 0.001), higher values for HbA1c (9.6 ± 1.7 vs. 8.2 ± 1.3%; p = 0.01) and lower values for BMI (24.3 ± 4.1 vs. 27.2 ± 2.6 kg/m2; p = 0.02), body fat percentage (26.6 ± 6.2 vs. 30.8 ± 7.7%; p = 0.04), and waist circumference (78.7 ± 8 vs. 85.8 ± 8.1 cm; p = 0.02). No association was found between the symptoms and the presence of Helicobacter pylori. Conclusions Dyspepsia symptoms in patients with long-standing DM1 were associated with glycemic control and depression, and they seem to negatively influence the nutritional status of these patients. .