Association between an increase in blood urea nitrogen at 24 hours and worse outcomes in acute nonvariceal upper GI bleeding.

BACKGROUND AND AIMS: An increase in blood urea nitrogen (BUN) at 24 hours is a solitary and significant predictor of mortality in patients with acute pancreatitis, which may predict worse outcomes in the similarly resuscitation-requiring condition of acute nonvariceal upper GI bleeding (UGIB). The aim of our study was to assess whether an increase in BUN at 24 hours is predictive of worse clinical outcomes in acute nonvariceal UGIB. METHODS: A retrospective cohort study including patients admitted to an academic hospital from 2004 to 2014 was conducted. An increase in BUN was defined as an increase in BUN at 24 hours of hospitalization compared with BUN at presentation. The primary outcome was a composite of inpatient death, inpatient rebleeding, need for surgical or radiologic intervention, or endoscopic reintervention. Associations between BUN change and outcomes were assessed via the Pearson χ2 test and the Fisher exact test and via logistic regression for adjusted analyses. RESULTS: There were 357 patients included in the analysis with a mean age of 64 years; 54% were men. The mean change in BUN was -10.1 mg/dL (standard deviation, 12.7 mg/dL). Patients with an increased BUN (n = 37 [10%]) were significantly more likely to experience the composite outcome (22% vs 9%, P = .014), including an increased risk of inpatient death (8% vs 1%, P = .004), compared with patients with a decreased or unchanged BUN (n = 320 [90%]). In a logistic regression model adjusting for the AIMS65 score, an increase in BUN was independently associated with an increased risk for the composite outcome (odds ratio, 2.75; P = .026). CONCLUSION: Increasing BUN at 24 hours likely reflects under resuscitation and is a predictor of worse outcomes in patients with acute nonvariceal UGIB.

Relationship of time to presentation after onset of upper GI bleeding with patient characteristics and outcomes: a prospective study.

BACKGROUND AND AIMS: We performed a prospective multi-national study of patients presenting to the emergency department with upper GI bleeding (UGIB) and assessed the relationship of time to presentation after onset of UGIB symptoms with patient characteristics and outcomes. METHODS: Consecutive patients presenting with overt UGIB (red-blood emesis, coffee-ground emesis, and/or melena) from March 2014 to March 2015 at 6 hospitals were included. Multiple predefined patient characteristics and outcomes were collected. Rapid presentation was defined as ≤6 hours. RESULTS: Among 2944 patients, 1068 (36%) presented within 6 hours and 576 (20%) beyond 48 hours. Significant independent factors associated with presentation ≤6 hours versus >6 hours on logistic regression included melena (odds ratio [OR], 0.22; 95% CI, 0.18-0.28), hemoglobin ≤80 g/L (OR, 0.47; 95% CI, 0.36-0.61), altered mental status (OR, 2.06; 95% CI, 1.55-2.73), albumin ≤30 g/L (OR, 1.43; 95% CI, 1.14-1.78), and red-blood emesis (OR, 1.29; 95% CI, 1.06-1.59). Patients presenting ≤6 hours versus >6 hours required transfusion less often (286 [27%] vs 791 [42%]; difference, -15%; 95% CI, -19% to -12%) because of a smaller proportion with low hemoglobin levels, but were similar with regard to hemostatic intervention (189 [18%] vs 371 [20%]), 30-day mortality (80 [7%] vs 121 [6%]), and hospital days (5.0 ± 0.2 vs 5.0 ± 0.2). CONCLUSIONS: Patients with melena alone delay their presentation to the hospital. A delayed presentation is associated with a decreased hemoglobin level and increases the likelihood of transfusion. Other outcomes are similar with rapid versus delayed presentation. Time to presentation should not be used as an indicator for poor outcome. Patients with delayed presentation should be managed with the same degree of care as those with rapid presentation.

Quantitative LC-MS/MS Glycomic Analysis of Biological Samples Using AminoxyTMT.

Protein glycosylation plays an important role in various biological processes, such as modification of protein function, regulation of protein-protein interactions, and control of turnover rates of proteins. Moreover, glycans have been considered as potential biomarkers for many mammalian diseases and development of aberrant glycosylation profiles is an important indicator of the pathology of a disease or cancer. Hence, quantitation is an important aspect of a comprehensive glycomics study. Although numerous MS-based quantitation strategies have been developed in the past several decades, some issues affecting sensitivity and accuracy of quantitation still exist, and the development of more effective quantitation strategies is still required. Aminoxy tandem mass tag (aminoxyTMT) reagents are recently commercialized isobaric tags which enable relative quantitation of up to six different glycan samples simultaneously. In this study, liquid chromatography and mass spectrometry conditions have been optimized to achieve reliable LC-MS/MS quantitative glycomic analysis using aminoxyTMT reagents. Samples were resuspended in 0.2 M sodium chloride solution to promote the formation of sodium adduct precursor ions, which leads to higher MS/MS reporter ion yields. This method was first evaluated with glycans from model glycoproteins and pooled human blood serum samples. The observed variation of reporter ion ratios was generally less than 10% relative to the theoretical ratio. Even for the highly complex minor N-glycans, the variation was still below 15%. This strategy was further applied to the glycomic profiling of N-glycans released from blood serum samples of patients with different esophageal diseases. Our results demonstrate the benefits of utilizing aminoxyTMT reagents for reliable quantitation of biological glycomic samples.

The relationship between clinical findings and esophageal injury severity in children with corrosive agent ingestion.

BACKGROUND: The aim of the study was to investigate the indicators of corrosive esophageal injury (EI) severity in children. METHODS: We retrospectively reviewed data from children who accidentally ingested corrosive substance and underwent endoscopic evaluation over a one-year period. A total of 134 consecutive children with corrosive agent ingestion who underwent diagnostic endoscopy (74 boys, 60 girls) were included in this study. Patients were divided into two groups as low-grade and high-grade EI. Statistical differences and predictive values of common signs and symptoms and white blood cell (WBC) count of patients with low- and high-grade EI were analyzed. RESULTS: The majority of patients (70%) were asymptomatic at the initial examination. We found that drooling saliva and oral lesions were significantly more frequent in high-grade injury (p<0.05). Mean WBC count in the high-grade EI group was significantly higher than in the low-grade EI group (p=0.000). Sensitivity, specificity and predictive values of clinical findings in children were analyzed; none of them was shown to be valuable for estimating EI severity. WBC count was sensitive, but it is not a good predictor. CONCLUSION: Our study demonstrated the relationship between clinical findings and corrosive EI severity in children with accidental corrosive ingestion, but direct visualization of the esophagus is required for definitive diagnosis.

Influence of route of gastric transposition on oxygen supply at cervical oesophagogastric anastomoses.

BACKGROUND: The microcirculation and oxygen supply at the oesophagogastric anastomosis are crucial factors that influence anastomotic healing after oesophagectomy. METHODS: Twenty-nine patients (mean age 61.7 years) underwent gastric transposition via an orthotopic (14) or retrosternal (15) route. Interstitial partial pressure of oxygen (PO2) of the stomach in the anastomotic region was measured during oesophagectomy and in the intensive care unit. Interstitial PO2 values were determined after ligation of the short gastric vessels, after ligation of the left gastric artery, after forming the conduit and after gastric transposition. Postoperative measurements were recorded during endotracheal intubation, while breathing oxygen by mask or through the nose, and while breathing air. RESULTS: Interstitial PO2 levels were significantly higher before ligation of the left gastric artery than after ligation (mean 76.1 (95 per cent confidence interval 54.9 to 103.1) versus 44.9 (24.6 to 77.1) mmHg; P = 0.001). Levels were also higher following orthotopic transposition compared with the retrosternal route (68.2 (44.0 to 118.8) versus 24.6 (10.7 to 39.4) mmHg; P = 0.001) and during each postoperative measurement period. No differences were found between the various oxygen supply systems. CONCLUSION: Oxygen supply at the anastomosis of the gastric conduit reaches higher levels after orthotopic than retrosternal gastric transposition.

Plasma nuclear DNA and mitochondrial DNA as prognostic markers in corrosive injury patients.

STUDY OBJECTIVES: Ingestion of a corrosive substance produces an injury to the gastrointestinal tract and it is often difficult to evaluate the severity and prognosis of this injury. Increased concentrations of plasma nuclear DNA and mitochondrial DNA (mtDNA) have been found to be associated with the area of corrosion. This study examined the level of plasma DNA as it relates to the severity of corrosive injury. METHODS: Forty-eight consecutive patients were enrolled prospectively. The concentrations of plasma nuclear DNA and mtDNA were measured by real-time quantitative polymerase chain reaction assay at presentation to the emergency room and 12 h later. RESULT: The median age of the patients enrolled was 55 years (20 men and 28 women) with an overall mortality rate of 21%. Nineteen patients underwent operative intervention secondary to perforation. Findings included significantly elevated plasma nuclear DNA and mtDNA in the mortality group at presentation and 12 h after injury compared to the survival group. CONCLUSION: The concentrations of plasma nuclear DNA and mtDNA were elevated within 4 h after corrosive injury. The elevated concentrations of plasma nuclear DNA and mtDNA could be useful prognostic markers to correlate with the clinical outcome in corrosive patients.

A non-invasive method for the diagnosis of upper GI diseases.

Upper-GI diseases are one of the most relevant issue in primary care. Nowadays they are still responsible for about 100 million ambulatory care visits only in the US. The diagnosis of almost every upper-GI condition is still deputed to invasive tests such as upper gastrointestinal endoscopy, gastroesophageal manometry or radiography. The possibility of analysing serum markers like Pepsinogens I and II, produced by gastric mucosa, in order to assess the functional characteristics of the upper GI tract has spread itself since the 80's especially in the diagnosis of peptic ulcer. The discovery of Helicobacter pylori by Marshall and Warren in 1983 and the scientific consecration of its role in the pathogenesis of gastric cancer and peptic ulcer (crystallized in Peleo Correa's Cascade, 1992), led to an increase importance of non-invasive tests, raising the attention towards the assessment of both immunoglobulins anti-H.p. and Gastrin hormone produced by antral G cells, as an implementation of the panel of gastric markers. This narrative review aims to analyze the huge landscape of non-invasive tests for diagnosis of GI diseases, studying the literature of the recent years.

Utility of 15(S)-HETE as a Serological Marker for Eosinophilic Esophagitis.

The pathogenesis of eosinophilic esophagitis (EoE) involves Th2-mediated eosinophil recruitment and degranulation into the esophagus. However, measuring serum Th2 cytokines, eosinophils, and eosinophil-derived products does not reliably distinguish EoE from control populations. Non-invasive methods to diagnose EoE are lacking. We evaluated the diagnostic value of a novel candidate biomarker of EoE: 15(S)-hydroxyeicosatetraenoic acid (HETE). We used immunoassay to measure 15(S)-HETE and cytokine profiles in patients undergoing endoscopy with known or suspected EoE. 31 subjects were enrolled, 16 with EoE, and 15 with an alternate diagnosis. 15(S)-HETE was elevated in the EoE group compared to non-EoE group. The sensitivity and specificity of 15(S)-HETE to be used as a non-invasive marker is 50% and 80%, respectively. 15(S)-HETE may aid in the diagnosis of EoE.

Is glycogenic acanthosis a predictor of insulin resistance and metabolic syndrome?

BACKGROUND/AIMS: To evaluate the incidence of insulin resistance and metabolic syndrome (MetS) in patients with glycogenic acanthosis (GA). MATERIALS AND METHODS: Thirty patients with GA, detected upon endoscopy, and 30 age- and sex-matched control patients without GA were included in this case-control study. Patients with GA were considered group 1 and control group was considered group 2. Anthropometric measurements [height, weight, and waist circumference (WC)], biochemical parameters [fasting plasma glucose (FPG), triglyceride, high-density lipoprotein (HDL), and low-density lipoprotein (LDL)], and serum fasting insulin levels were evaluated. Insulin resistance (IR) was estimated by the homeostatic model assessment of IR. MetS was diagnosed using the criteria of the National Cholesterol Education Program Adult Treatment Panel III. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated to evaluate associations with GA. RESULTS: There were no differences in terms of FPG, triglyceride, HDL, and LDL between groups (p-values 0.118, 0.114, 0.192, 0.086, respectively). WC was significantly higher in group 1 than in group 2 (103.77 vs 97.03, p=0.032). The number of patients with IR and MetS were significantly higher in group 1 than in group 2 (53.3% vs 13.3%, p=0.003 and 53.3% vs 23.3%, p=0.034). ORs [95% CI] of WC, IR, and MetS for GA were 0.68 [0.17-2.62], 7.12 [1.89-26.72], and 4.11 [1.04-16.21], respectively. CONCLUSION: These findings showed that IR and MetS were significantly associated with the presence of GA.

Analysis of tissue and circulating microRNA expression during metaplastic transformation of the esophagus.

Genetic changes involved in the metaplastic progression from squamous esophageal mucosa toward Barrett's metaplasia and adenocarcinoma are almost unknown. Several evidences suggest that some miRNAs are differentially expressed in Barrett's esophagus (BE) and esophageal adenocarcinoma. Among these, miR-143, miR-145, miR-194, miR-203, miR-205, miR-215 appear to have a key role in metaplasia and neoplastic progression. The aim of this study was to analyze deregulated miRNAs in serum and esophageal mucosal tissue biopsies to identify new biomarkers that could be associated with different stages of esophageal disease. Esophageal mucosal tissue biopsies and blood samples were collected and analyzed for BE diagnosis. Quantitative Real-time PCR was used to compare miRNA expression levels in serum and 60 disease/normal-paired tissues from 30 patients diagnosed with esophagitis, columnar-lined esophagus (CLO) or BE. MiRNA expression analysis showed that miR-143, miR-145, miR-194 and miR-215 levels were significantly higher, while miR-203 and miR-205 were lower in BE tissues compared with their corresponding normal tissues. Esophageal mucosa analysis of patients with CLO and esophagitis showed that these miRNAs were similarly deregulated but to a lesser extent keeping the same trend and CLO appeared as intermediate step between esophagitis and BE. Analysis on circulating miRNA levels confirmed that miR-194 and miR-215 were significantly upregulated in both BE and CLO compared to esophagitis, while miR-143 was significantly upregulated only in the Barrett group. These findings suggest that miRNAs may be involved in neoplastic/metaplastic progression and miRNA analysis might be useful for progression risk prediction as well as for monitoring of BE/CLO patients.

Characteristics of HIV-infected men with low serum testosterone levels.

Low levels of serum testosterone may have negative implications on morbidity in HIV-infected men. The purpose of this study was to determine demographic and clinical characteristics that predict low serum testosterone among men attending our HIV clinic. A cross-sectional study of 587 HIV-positive male patients who presented at the Louisiana State University HIV Outpatient (HOP) Clinic between August 1997 and January 1999 was conducted. Demographic and clinical characteristics were collected and analysed. Of the 587 men studied, 119 (20.3%) had a serum testosterone level below 400 ng/dl. Significantly more men with low serum testosterone levels had a presence of opportunistic infection (especially HIV wasting syndrome, oesophageal candidiasis, or dementia), CD4+ cell counts below 200 cells/mm3, or were taking megestrol acetate. Early detection of low serum testosterone will allow for expedient testosterone supplementation therapy, which could improve morbidity and quality of life for HIV-infected men.

Spontaneous esophageal rupture: a frequently missed diagnosis.

The objective of this study was to determine the diagnostic features of spontaneous esophageal rupture and compare them with those traditionally applied in making this diagnosis. A retrospective 15-year chart review was performed on all cases listing esophageal rupture as a diagnosis. Only those cases diagnosed by contrast studies or direct visual confirmation were included. Facets of the history, physical examination, laboratory results, and X-ray procedures were examined and compared with the "classic" presentation of this diagnosis as noted in current medical texts. Fourteen cases of confirmed esophageal rupture were found. Only a small minority of cases presented in a fashion resembling a classic case. Esophageal rupture was the admitting diagnosis in 29 per cent of the cases. Laboratory values associated with esophageal rupture included elevated white blood cell count and hypoxia. The chest X-ray was abnormal in all but one patient, with findings of pneumothorax and/or pleural effusion in the majority. We conclude that reliance on classic findings will lead to misdiagnosis in the vast majority of cases presenting to the Emergency Department. Conversely, toxic appearance, pleural effusion, pneumothorax, elevated white blood cell count, azotemia, and hypoxia are all positively associated with this disease. In toxic-appearing patients with pleural effusions and/or pneumothoraces, spontaneous esophageal rupture should be considered.

Immunologic detection of fecal occult blood from upper digestive tract diseases.

BACKGROUND/AIMS: This study was conducted to evaluate the accuracy of the immunochemical occult blood test for upper digestive tract diseases. METHODOLOGY: The test was performed on 226 subjects, including 124 upper digestive tract diseases (12 ulcerative esophagitis cases, 10 esophageal cancer cases, 33 gastric ulcer cases, 33 gastric cancer cases, and 36 duodenal ulcer cases), 34 colorectal cancer cases, and 68 healthy subjects, after which, the accuracy of this test was evaluated. RESULTS: The test was positive 23 in upper digestive tract diseases (2 in ulcerative esophagitis, 2 in esophageal cancer, 5 in gastric ulcer, 8 in gastric cancer, 6 in duodenal ulcer), 31 in colorectal cancer, and 3 in healthy subjects, respectively. Thus, the sensitivity was 19% for upper digestive tract diseases (16.7% for ulcerative esophagitis, 20% for esophageal cancer, 15% for gastric ulcer, 24% for gastric cancer, 20% for duodenal ulcer) and 91% for colorectal cancer, and the specificity was 96%. Significant difference was noted in the sensitivity between upper digestive tract diseases and colorectal cancers (p0.001), whereas there was no difference among 5 upper digestive tract diseases. CONCLUSIONS: These results indicate that the immunochemical occult blood is inadequate as means for detection of upper digestive tract diseases, and that an examination of upper digestive tract is unnecessary in cases where the immunochemical occult blood test is positive, but there is no evidence of diseases in colon and rectum.

Trypanosoma cruzi prevalence and clinical forms in blood donor candidates in Brazil.

The prevalence and clinical forms of Trypanosoma cruzi were evaluated among blood donor candidates attended at a general hospital in Rio de Janeiro, Brazil, from January 1997 to April 1999. The investigation was done by means of the indirect hemagglutination test and was confirmed via ELISA. Data were collected from clinical examinations, conventional electrocardiogram, chest radiography and echocardiography. The results showed that despite Trypanosoma cruzi prevalence of 1.17% (128 patients), mainly in males aged 40 years or over, 70.8% of these patients, mainly males aged 19 to 39 years, demonstrated abnormalities that allowed the diagnosis of cardiopathy and/or esophagopathy. This once again corroborates the importance of Trypanosoma cruzi infection in urban centers.

[Gastric xanthomatosis in a patient with severe lipid metabolic disorder]. / Xantomatosi gastrica in paziente con grave dismetabolismo lipidico.

Gastric xanthomas are rare in routine endoscopy, generally ranging from to 2 to 5 mm in diameter, mostly isolated, but in some cases multiple. Their nature has not yet been cleared. In fact, even if they have histochemical characteristics similar to cutaneous xanthelasmas, they are not generally considered closely related to lipid metabolism disorders. The Authors report a case with some peculiarities regarding number, location and dimension of the gastric xanthomas, and point out the possibility of a metabolic disorder in their aetiopathogenesis.

[Characteristics of thrombocyte aggregation properties in portal hypertension syndrome complicated by esophagogastric hemorrhage]. / Osobennosti agregatsionnykh svoistv trombotsitov pri sindrome portal'noi gipertenzii, oslozhnennom pishchevodno-zheludochnymi krovotecheniiami.

An investigation of ADP-induced aggregation of thrombocytes in 62 patients with the portal hypertension syndrome has revealed pronounced functional alterations of blood platelets characterized by a lower aggregation rate, lower rate and degree of thrombocyte deaggregation. More profound alterations were found in patients with cirrhosis of the liver. It was established that the decreased rate and degree of the thrombocyte deaggregation with the growing aggregation rate, change of the aggregation into the irreversible form is a very dangerous portent of gastrointestinal bleeding.

Factors associated with esophageal candidiasis and its endoscopic severity in the era of antiretroviral therapy.

BACKGROUND: Candidia esophagitis (CE) is an AIDS-defining condition, usually occurring in individuals with low CD4 counts of <200 cells/µL. Endoscopy is a valuable definitive diagnostic method for CE but may not be indicated for asymptomatic patients or for those with high CD4 counts or without oral candidiasis. This study assessed such patients to clarify the factors associated with CE and its severity on endoscopy in the highly active antiretroviral therapy (HAART) era. METHODOLOGY PRINCIPAL FINDINGS: A total of 733 HIV-infected patients who underwent upper gastrointestinal (GI) endoscopy were analyzed. Sexual behavior, CD4(+) count, HIV-RNA viral load (VL), history of HAART, GI symptoms, GI diseases, and oral candidiasis were assessed. Endoscopic severity of CE was classified as mild (Kodsi's grade I/II) or severe (grade III/IV). Of the 733 subjects, 62 (8.46%) were diagnosed with CE (mild, n = 33; severe, n = 29). Of them, 56.5% (35/62) had no GI symptoms, 30.6% (19/62) had CD4 + ≥200 cells/µL, and 55.3% (21/38) had no oral candidiasis. Univariate analysis found lower CD4+ counts, higher HIV VL, and no history of HAART to be significantly associated with CE. With lower CD4(+) counts and higher HIV VL, CE occurrence increased significantly (P<0.01 for trend in odds). Multivariate analysis showed low CD4+ counts and high HIV VL to be independently associated with CE. Of the severe CE patients, 55.2% (16/29) had no GI symptoms and 44.4% (8/18) had no oral candidiasis. Median CD4(+) counts in severe cases were significantly lower than in mild cases (27 vs. 80; P = 0.04). CONCLUSIONS: Low CD4+ counts and high HIV VL were found to be factors associated with CE, and advanced immunosuppression was associated with the development of severity. Endoscopy is useful as it can detect CE, even severe CE, in patients without GI symptoms, those with high CD4 counts, and those without oral candidiasis.

Serum alkaline phosphatase activity is not a marker for neoplastic transformation of esophageal nodules in canine spirocercosis.

BACKGROUND: Spirocerca lupi is a nematode of Canidae that matures within the esophageal wall to form fibroblastic nodules with potential for malignant transformation. Diagnosis is based on histopathologic examination, but false-negative results may be obtained from samples collected by endoscopy. Serum alkaline phosphatase (ALP) activity, frequently increased in hepatobiliary disease, is also increased in a variety of neoplastic conditions in dogs, including appendicular osteosarcoma, and has also been reported to be increased in dogs with spirocercosis. OBJECTIVE: The aim of this study was to evaluate serum ALP activity as a marker for malignant transformation of esophageal nodules in S. lupi-infected dogs. METHODS: In this retrospective study, medical records of dogs diagnosed with spirocercosis from 1991 to 2008 were reviewed, and serum ALP activity determined at presentation was compared between dogs with nonneoplastic and neoplastic nodules. Owing to use of multiple analyzers, ratios of ALP activity to the upper reference interval for ALP were calculated and compared. RESULTS: Median ALP activity ratios were 0.65 (0.07-4.00) and 0.86 (0.10-3.40) for dogs with nonneoplastic (n=88) and neoplastic (n=32) nodules, respectively, with no significant difference (P=.18) and substantial overlap between groups. Tumors included osteosarcoma (15 dogs), fibrosarcoma (15 dogs), and anaplastic sarcoma (2 dogs); there was no difference in ALP activity between the dogs with osteosarcoma and fibrosarcoma. CONCLUSION: ALP is a poor marker of malignant transformation in canine spirocercosis.