The Role of Endoscopic Retrograde Cholangiopancreatography in the Diagnosis of Biliary Atresia: 14 Years' Experience.

INTRODUCTION: Biliary atresia (BA) is a rare destructive inflammatory obliterative cholangiopathy of neonates. Early diagnosis is important in disease management. The aim was to evaluate the role of endoscopic retrograde cholangiopancreatography (ERCP) in diagnosing BA in a large cohort. In addition, we evaluated whether parameters such as bile trace, GGT, bilirubin, and laboratory values in combination can be used to develop a risk score that could indicate the referral to specialized centers. MATERIALS AND METHODS: All infants with neonatal cholestasis (2000-2014) who presented to our endoscopy unit for suspected BA were included. Demographics, laboratory parameters, ultrasound findings, liver biopsy results, ERCP diagnosis, and surgical outcome were collected. Value and safety of ERCP and risk factors for BA were retrospectively analyzed. RESULTS: We included 251 infants in our cohort (55% males, median age: 53 days). BA was intraoperatively diagnosed in 155 (83.4%) patients and was excluded in 30 (16.2%). Fifty-six cases were not operated due to the ERCP findings. ERCP was successful in 224/251 patients (89.2%) with no procedure-related complications. The operative and endoscopic diagnosis matched in 96.6% of the patients (positive predictive value: 92.2%, negative predictive value: 97.1%). In comparison to cases with excluded BA, the ones with this disease were significantly associated with absence of duodenal bile traces (98.4 vs. 1.6%, p < 0.001), higher bilirubin (p < 0.001, cutoff 7.3 mg/dL), and higher GGT (p < 0.001, cutoff 250 U/L). CONCLUSION: ERCP is safe and accurate in the hands of experts in diagnosing BA if the cause of cholestasis is unclear. While evaluating the role of ERCP for diagnosing this disease, we found that the secondary parameters GGT > 250 U/L, bilirubin > 7.3 mg/dL (125 µmol/L), and the absence of bile traces are risk factors.

Quality of Life and Nutrition Condition of Patients Improve Under Home Parenteral Nutrition: An Exploratory Study.

BACKGROUND: Patients with end-stage cancer and advanced chronic bowel disease are often malnourished, which has a negative effect on patients' outcome, well-being, and activity. It is inconclusive whether these patients benefit from home parenteral nutrition. This prospective exploratory study investigates its influence on nutrition state, muscle strength, mobility, and quality of life. MATERIALS AND METHODS: Patients ≥18 years old with an indication for home parenteral nutrition were included and followed for 2-24 months. Nutrition parameters, activity, and quality of life were assessed. RESULTS: Forty-eight patients participated (mean age 11.5 years), and 85% were severely malnourished (subjective global assessment score, class C). Four weeks after parenteral nutrition, patients with tumors demonstrated a deterioration in phase angle (from 3.9 to 3.4) and extracellular mass:body cell mass ratio (from 1.6 to 2.1), while patients with bowel disease improved (from 3.4 to 4.0 and 2.1 to 1.6, respectively); grip strength remained constant in both groups (difference: 1.11 and -2.11, respectively). Activity improved in patients with bowel disease but stayed the same in the tumor group (P = .02 and P = .33, respectively). When the groups were pooled, emotional and social functioning domain scores (P < .03), dyspnea and sleeping (P < .04), and median quality of life improved (P = .02) 4 weeks after home parenteral nutrition. CONCLUSION: Both groups seem to benefit from home parenteral nutrition without harmful side effects. If the indication is determined early, the patients' disease course could perhaps be improved.

Complication and mortality rate after percutaneous endoscopic gastrostomy are low and indication-dependent.

OBJECTIVE: Percutaneous endoscopic gastrostomy (PEG) is often used for the feeding of patients with malnutrition due to dysphagia, and despite more than 30 years experience, numerous questions on its benefit remain. This was a prospective observational study to assess the safety of PEG. MATERIAL AND METHODS: One hundred and nineteen patients mean age 63 years (21-91 years) who were admitted to the Hannover Medical School between November 2010 and March 2012 and had an indication for PEG according to the German guidelines were included. Primary endpoints were the following: reason for indication, date of in-hospital mortality after PEG insertion, death within 3 months after PEG placement, and complications. RESULTS: Most patients (54.6%) received PEG for dysphagia caused by tumors and second (29.4%) for neurologic diseases with a minor proportion of dementia (3%). About 73% of our patients had no complications at all and only 10% suffered severe effects. We saw only 1 case of aspiration, which did not lead to pneumonia. The 30-day mortality was 10%, and no patient died as a result of the PEG procedure. Significantly more patients with neurologic disorders died within 24 weeks of PEG placement than tumor patients (60% versus 27.7%, respectively, p = 0.002, n = 100). CONCLUSION: It is important to select patients receiving PEG very carefully. The patients' indications, their primary disease, and their capability for mental cooperation are essential. If these aspects are taken into account, PEG is a safe method with few mainly mild complications.

Assessment of xylitol serum levels during the course of parenteral nutrition including xylitol in intensive care patients: a case control study.

BACKGROUND & AIMS: Xylitol has been approved for parenteral nutrition and may be beneficial in catabolic situations. The aim was to establish an easy method to monitor xylitol serum levels in patients receiving xylitol and to determine whether xylitol is safe. METHODS: A commercially available xylitol test was validated and used to measure serum levels in 55 patients admitted to our intensive care unit with an indication for parenteral nutrition with xylitol for at least 24 h. Controls consisted of the most recent 56 patients admitted to the intensive care unit who received parenteral nutrition without xylitol for at least 2 days. Xylitol serum levels were determined using the test. Adverse events, liver enzymes, lactate, bilirubin, γ-glutamyl transpeptidase, and insulin requirement were secondary endpoints. RESULTS: Patients receiving xylitol received 32.6% less insulin than controls. The amount of energy they received was comparable (xylitol: 810.1; controls: 789.8 kcal). Mean liver enzymes and lactate levels were similar in both groups. Adverse events considered attributable to xylitol did not occur. Xylitol did not accumulate in patients' blood and returned to near baseline values one day after parenteral nutrition was stopped. CONCLUSIONS: Parenteral nutrition with xylitol appears to be safe for critical care patients. There were no signs of hepatoxicity. TRIAL REGISTRATION DRKS: DRKS00004238.

Tolerability and efficacy of a low-volume enteral supplement containing key nutrients in the critically ill.

BACKGROUND & AIMS: To compare early supplementation with antioxidants and glutamine using a low-volume enteral supplement containing key nutrients to an energy adjusted standard elementary diet and to investigate its effect on clinical efficacy and tolerability in critically ill patients with sepsis/SIRS. The primary endpoints were length of stay in the ICU and sufficient enteral feed. METHODS: This was a randomized, prospective, single-blind, controlled study in 58 critically ill patients (56.9% male, mean age 46.7 years, mean APACHE II score 21.6). They received either a low-volume enteral supplement containing key nutrients or a diluted standard nutrition solution. After 10 or 14 days inflammatory parameters, catecholamine need, and maximal enteral delivery were determined. RESULTS: Patients receiving a low-volume enteral supplement containing key nutrients did not reach sufficient enteral feed more often than controls (76 vs. 62%, respectively, p = 0.17). The difference in vitamin E and selenium uptake was higher in the treatment group than controls (12.4 vs. 3.7 and 54.7 vs. 16.3, respectively, p ≤ 0.011). Parameters such as fever, antibiotic treatment, artificial ventilation, and death were comparable. This was also true for days of ICU or hospital stay (33 ± 23 and 49 ± 34 days, respectively). CONCLUSIONS: The low-volume enteral supplement containing key nutrients was well tolerated and led to a better vitamin E and selenium supply. However, it did not affect length of ICU or hospital stay. Further studies are necessary to determine which disease-specific subgroups may benefit from this supplementation or which group may be harmed.

Endotoxin augments myeloid dendritic cell influx into the airways in patients with allergic asthma.

RATIONALE: Epidemiologic studies have shown that exacerbation of asthma is modulated by environmental endotoxin. High levels of endotoxin are associated with asthma symptoms and the current use of asthma medication. However, the underlying mechanisms by which endotoxin modulates asthma are not completely understood. OBJECTIVES: The aim of the study was to test whether endotoxin enhances the response of individuals with allergic asthma to allergen, and to determine if this interaction is associated with increased numbers of antigen-presenting cells in the airways. METHODS: Seventeen subjects with mild allergic asthma underwent segmental challenge with allergen, endotoxin, and the combination of both in three different lung segments via bronchoscopy. The cellular influx including monocytes, myeloid dendritic cells (mDCs), and plasmacytoid dendritic cells (pDCs), as well as the level of cytokines, were assessed in bronchoalveolar lavage fluid obtained 24 hours after segmental challenge. Monocytes, mDCs, and pDCs were isolated and their capacity to induce T cell proliferation was determined. MEASUREMENTS AND MAIN RESULTS: Endotoxin enhanced the cellular response to allergen. The combination of allergen and endotoxin resulted in increased numbers of total cells, lymphocytes, neutrophils, eosinophils, monocytes, and mDCs, as well as increased levels of lipopolysaccharide-binding protein, IL-1alpha, IL-6, and tumor necrosis factor-alpha in the bronchoalveolar lavage fluid compared with allergen alone. Isolated mDCs but not pDCs induced a strong T cell proliferation in vitro. CONCLUSIONS: Endotoxin augments the allergic inflammation in the lungs of individuals with asthma, and induces an enhanced influx of monocytes and functionally active antigen-presenting mDCs into the respiratory tract.

Facial thermography is a sensitive tool to determine antihistaminic activity: comparison of levocetirizine and fexofenadine.

AIMS: To assess the antihistaminic activity of levocetirizine and fexofenadine 2 h and 24 h after drug administration using facial thermography and to compare the results with those using well-established parameters of antihistaminic activity in the nose and skin. METHODS: This was a randomized, double-blind, three-treatment, three-period, single-dose, cross-over study in healthy males taking levocetirizine 5 mg, fexofenadine 120 mg or placebo. The primary endpoint was nasal skin temperature after nasal histamine challenge recorded for 20 min at 2 and 24 h after drug intake. The secondary endpoints were nasal symptoms and a histamine skin prick test. RESULTS: Thirty subjects were randomized. At 2 h after drug intake the inhibition of the nasal temperature increase from baseline was not significantly different between levocetirizine and fexofenadine. At 24 h it was significantly more pronounced after levocetirizine than fexofenadine (difference: least-squares mean: -0.13 degrees C; P < or = 0.024, 95% CI -0.24, -0.02). Both drugs significantly reduced (P < or = 0.001) the mean temperature increase from baseline compared with placebo at 2 and 24 h (least-squares mean increase and (95% CI): levocetirizine, -0.28 degrees C (-0.42, -0.14) and -0.32 degrees C (-0.43, -0.21); fexofenadine -0.35 degrees C (-0.49, -0.21) and -0.19 degrees C (-0.30, -0.08), respectively). Results of nasal symptom score and wheal and flare were consistent with the thermography results. CONCLUSIONS: Facial thermography is an objective, non-invasive and sensitive method to study antihistaminic activity at the nose level. Levocetirizine and fexofenadine demonstrate the same activity at 2 h after drug intake, but levocetirizine has a more sustained activity at 24 h.

Local nitric oxide levels reflect the degree of allergic airway inflammation after segmental allergen challenge in asthmatics.

Nitric oxide (NO) levels are increased in the exhaled air of asthmatics. As NO levels correlate with allergic airway inflammation, NO measurement has been suggested for disease monitoring. In patients with asthma, we previously demonstrated that intrabronchial treatment with a natural porcine surfactant enhanced airway inflammation after segmental allergen provocation. We studied whether local levels of NO reflect the degree of allergic airway inflammation following segmental allergen challenge with or without surfactant pretreatment. Segmental NO, as well as nitrite and nitrate in bronchoalveolar lavage (BAL) fluid, was measured before and after segmental challenge with either saline, saline plus allergen, or surfactant plus allergen in 16 patients with asthma and five healthy subjects. The data were compared with inflammatory BAL cells. Segmental NO levels were increased after instillation of saline (p < 0.05), or surfactant plus allergen in asthmatics (p < 0.05), and values were higher after surfactant plus allergen compared to saline challenge. Nitrate BAL levels were not altered after saline challenge but increased after allergen challenge (p < 0.05) and further raised by surfactant (p < 0.05), whereas nitrite levels were not altered by any treatment. Segmental NO and nitrate levels correlated with the degree of eosinophilic airway inflammation, and nitrate levels also correlated with neutrophil and lymphocyte numbers in BAL. In healthy subjects, NO, nitrite, and nitrate were unaffected. Thus, segmental NO and nitrate levels reflect the degree of allergic airway inflammation in patients with asthma. Measurement of both markers can be useful in studies using segmental allergen provocation, to assess local effects of potential immunomodulators.

Metal-rich ambient particles (particulate matter 2.5) cause airway inflammation in healthy subjects.

Epidemiologic studies have shown an increased prevalence of allergic asthma in children living in a German smelter area (Hettstedt) compared with a cohort who live in a nonindustrialized area (Zerbst). However, it is not known whether ambient particles (particulate matter(2.5) [PM(2.5)]) from these areas induce distinct lung inflammation, which might be an explanation for this difference. Therefore, 100 microg of PM(2.5) suspensions, collected simultaneously in the two areas, were instilled through a bronchoscope into contralateral lung segments of 12 healthy volunteers. PM(2.5) from both Hettstedt and Zerbst increased the number of leukocytes in the bronchoalveolar lavage performed 24 hours later. PM(2.5) from Hettstedt, but not Zerbst, induced a significant influx of monocytes (Hettstedt: 7.0% vs. Zerbst: 4.3%) without influencing the expression of surface activation markers on monocytes and alveolar macrophages. Oxidant radical generation of bronchoalveolar lavage cells and cytokine concentration (interleukin-6 and tumor necrosis factor-alpha) in bronchoalveolar lavage fluid was significantly increased after instillation of Hettstedt PM(2.5). We conclude that environmentally relevant concentrations of PM(2.5) from the smelter area induced distinct airway inflammation in healthy subjects with a selective influx of monocytes and increased generation of oxidant radicals. The higher concentration of transition metals in PM(2.5) from Hettstedt might be responsible for this increased inflammation.