Abstract
Background and study aims
Gastrointestinal symptoms assumed to be caused by food intolerance are reported frequently in the general population. There is a significant difference between ...self-reported and objective proven food intolerance, as shown by placebo-controlled, double-blind, randomized trials. This discrepancy may be overcome by endoscopic confocal laser endomicroscopy (eCLE).
Patients and methods
In an observational study we evaluated 34 patients with functional abdominal pain and adverse reaction to food by eCLE and local duodenal food challenge for the first time. Spontaneous and food-induced transfer of fluorescein into the duodenal lumen was detected 10 minutes after intravenously application of fluorescein and 10 minutes after duodenal food challenge (DFC).
Results
Of the patients, 67.6 % responded with a fluorescein leakage into the duodenal lumen. Frequency rank order of food antigens that induced a response were soy (50 %), wheat (46.1 %), milk (20 %), egg (12 %), and yeast (11.5 %), respectively. Of the patients, 23.5 % showed spontaneous leakage of fluorescein, suggesting leaky gut syndrome. Histology of duodenal biopsies and mast cell function were normal. Overall, 69.5 % of patients improved with food exclusion therapy and 13 % were symptom-free according to eCLE.
Conclusions
The results of our study indicate that eCLE is a clinically useful tool to evaluate patients with functional abdominal pain and adverse reaction to food and to create individualized dietary therapy with clinical benefit for patients.
In healthy subjects repeated tactile stimulation in a conditioning test stimulation paradigm yields attenuation of primary (S1) and secondary (S2) somatosensory cortical activation, whereas a ...preceding painful stimulus results in facilitation.
Since previous data suggest that cognitive processes might affect somatosensory processing in S1, the present study aims at investigating to what extent cortical reactivity is altered by the subjective estimation of pain. To this end, the effect of painful and tactile stimulation on processing of subsequently applied tactile stimuli was investigated in patients with fibromyalgia syndrome (FMS) and in subjects with masochistic behaviour (MB) by means of a 122-channel whole-head magnetoencephalography (MEG) system. Ten patients fulfilling the criteria for the diagnosis of FMS, 10 subjects with MB and 20 control subjects matched with respect to age, gender and handedness participated in the present study. Tactile or brief painful cutaneous laser stimuli were applied as conditioning stimulus (CS) followed by a tactile test stimulus (TS) 500 ms later. While in FMS patients significant attenuation following conditioning tactile stimulation was evident, no facilitation following painful stimulation was found. By contrast, in subjects with MB no attenuation but significant facilitation occurred. Attenuation as well as facilitation applied to cortical responses occurring at about 70 ms but not to early S1 or S2 responses. Additionally, in FMS patients the amount of attenuation was inversely correlated with catastrophizing tendency.
The present results imply altered cortical reactivity of the primary somatosensory cortex in FMS patients and MB possibly reflecting differences of individual pain experience.
Endoscopic confocal laser endomicroscopy (eCLE) is an established technique that allows clinical evaluation of mucosal integrity by fluorescein leaking through the mucosa upon duodenal food challenge ...(DFC). Analysis of eCLE with DFC in eosinophilic esophagitis (EoE) would be interesting to evaluate epithelial barrier dysfunction also in other regions of the gastrointestinal tract and to characterize potential individual food allergens that trigger the esophageal inflammation.
In an observational and proof of concept study we evaluated 9 patients with histologically proven EoE by eCLE and DFC. Severity of symptoms were graduated according to the validated symptom-based EoE activity index. The endoscopic appearance of the esophagus was described according to the Endoscopic Reference Score System (ERERS). Spontaneous and food induced transfer of fluorescein into duodenal lumen were detected 10 minutes following intravenously application of fluorescein and 10 minutes after DFC. Food allergens were yeast, egg, soy, milk, and wheat, respectively. Local application of sodium chloride solution 10 % to the duodenal mucosa before DFC served as a control. Patients responding to DFC received a dietary exclusion therapy according to the results of DFC.
We investigated 9 patients with EoE (8 men, 49.7±13.8, 36-76 years). Symptom-based EoE activity index was 79±27.4, 33-100. In all patients EoE was confirmed by histology with number of esophageal mucosal eosinophilic granulocytes > 15/HPF, (91.4±77.4, 42-263). Mean ERERS score was 4.5±1.3, 3-7. None of the patients was aware of any food intolerance. eCLE revealed one patient with spontaneous transfer of i. v. fluorescein into duodenal lumen before DFC ("leaky gut"). 40 DFC were performed in the remaining 8 patients of whom 5 patients (61 %) responded to DFC. Rank order of fluorescein leakage upon DFC was wheat and milk in 37.5 % each, soy in 25 %, and egg in 12.5 %. The patients were treated by PPI (n=9), esophageal bouginage (n=5) and/or local corticoid therapy (n=3). The 5 patients responding to DFC received an additional food exclusion dietary advice focussed on the results of DFC. All patients reported a reduction of their symptoms. EoE activity indexes of patients with positive DFC were 73.7+28.6, 33-100 before and 22.7+37.9, 0-79 four weeks after food exclusion.
The findings of our proof of concept study suggest that eCLE with DFC may be an interesting tool to further evaluate patients with EoE. This technique has the potential to identify patients who may benefit from an additional individual dietary therapy.
Intramural pseudodiverticulosis of the esophagus (EIPD) is a rare disease leading to dysphagia, chest pain, and weight loss. The diagnosis is difficult, and the disease can be confounded with ...eosinophilic esophagitis (EoE). We present a patient with esophageal intramural pseudodiverticulosis and a literature review.
The 45-year-old white caucasian woman with a history of nicotine and alcohol abuse had progressive hoarseness and severe dysphagia for solid food. Esophagogastroduodenoscopy (EGD) showed proximal esophageal stenosis, thrush esophagitis, and mucosal alteration with trachealization suspicious of EoE. However, repeated bouginage EGD and barium swallow revealed typical signs of esophageal intramural pseudodiverticulosis (EIPD). The patient was treated successfully by bougingage, acid suppression, and antifungal therapy. The literature analysis revealed the characteristics of EIPD according to age, sex, risk factors, and therapy modalities.
The case report and the literature overview suggest that EIPD can be confounded with EoE.
The removal of bolus impaction within the esophagus is an indication for emergency endoscopy. The current guideline of the European Society of Gastrointestinal Endoscopy (ESGE) recommends gently ...pushing the bolus into the stomach. This view is discerned by many endoscopists because of the increased risk of complications. In addition, the use of an endoscopic cap for bolus removal is not mentioned.
In a retrospective analysis from 2017 to 2021 we investigated 66 adults and 11 children with acute bolus impaction within the esophagus.
Eosinophilic esophagitis, reflux esophagitic /peptic stenosis and Schatzki Ring caused 57.6%, esophageal and bronchial carcinoma 18%, esophageal motility disorders 4.5%, Zenkers diverticulum 1.5% and radiation esophagitis 1.5% of the bolus obstructions. The reason remained unclear in 16.7% of the cases. The spectrum was comparable in children with additional 2 cases with esophageal atresia and stenosis. The reason was unclear in 2 cases. Removal of bolus impaction was successful in 92.4% in adults and 100% in children. Bolus obstruction in adults was successfully removed solely by endoscopic cap in 57.6% and 75% in children. Pushing the bolus into the stomach without disintegration was possible in only 9% of cases.
Flexible endoscopy is an effective ermergency intervention for removal of bolus obstruction within the esophagus. Uncontrolled pushing the bolus into the stomach without view cannot be recommended. An endoscopic cap is a good extension for safe bolus removal.
Summary Background Comparative assessment of clinical outcomes after use of drug-eluting stents versus bare-metal stents for treatment of aortocoronary saphenous vein graft lesions has not been ...undertaken in large randomised trials. We aimed to undertake a comparison in a randomised trial powered for clinical endpoints. Methods In this randomised superiority trial, patients with de-novo saphenous vein graft lesions were assigned by computer-generated sequence (1:1:1:3) to receive either drug-eluting stents (one of three types: permanent-polymer paclitaxel-eluting stents, permanent-polymer sirolimus-eluting stents, or biodegradable-polymer sirolimus-eluting stents) or bare-metal stents. Randomisation took place immediately after crossing of the lesion with a guidewire, and was stratified for each participating centre. Investigators assessing data were masked to treatment allocation; patients were not masked to allocation. The primary endpoint was the combined incidence of death, myocardial infarction, and target lesion revascularisation at 1 year. Analysis was by intention to treat. This trial is registered at ClinicalTrials.gov , number NCT00611910. Findings 610 patients were allocated to treatment groups (303 drug-eluting stent, 307 bare-metal stent). Drug-eluting stents reduced the incidence of the primary endpoint compared with bare-metal stents (44 15% vs 66 22% patients; hazard ratio HR 0·64, 95% CI 0·44–0·94; p=0·02). Target lesion revascularisation rate was reduced by drug-eluting stents (19 7% vs 37 13% patients; HR 0·49, 95% CI 0·28–0·86; p=0·01). No significant differences were seen between drug-eluting stents and bare-metal stents regarding all-cause mortality (15 5% vs 14 5% patients; HR 1·08, 95% CI 0·52–2·24; p=0·83), myocardial infarction (12 4% vs 18 6%; HR 0·66, 95% CI 0·32–1·37; p=0·27), or definite or probable stent thrombosis (2 1% in both groups; HR 1·00, 95% CI 0·14–7·10; p=0·99). Interpretation In patients undergoing percutaneous coronary intervention for de-novo saphenous vein graft lesions, drug-eluting stents are the preferred treatment option because they reduce the risk of adverse events compared with bare-metal stents. Funding Deutsches Herzzentrum.
The combination of glycoprotein IIb/IIIa inhibitors and heparin has not been compared with bivalirudin in studies specifically involving patients with non-ST-segment elevation myocardial infarction ...undergoing percutaneous coronary intervention (PCI). We compared the two treatments in this patient population.
Immediately before PCI, we randomly assigned, in a double-blind manner, 1721 patients with acute non-ST-segment elevation myocardial infarction to receive abciximab plus unfractionated heparin (861 patients) or bivalirudin (860 patients). The study tested the hypothesis that abciximab and heparin would be superior to bivalirudin with respect to the primary composite end point of death, large recurrent myocardial infarction, urgent target-vessel revascularization, or major bleeding within 30 days. Secondary end points included the composite of death, any recurrent myocardial infarction, or urgent target-vessel revascularization (efficacy end point) and major bleeding (safety end point) within 30 days.
The primary end point occurred in 10.9% of the patients in the abciximab group (94 patients) and in 11.0% in the bivalirudin group (95 patients) (relative risk with abciximab, 0.99; 95% confidence interval CI, 0.74 to 1.32; P=0.94). Death, any recurrent myocardial infarction, or urgent target-vessel revascularization occurred in 12.8% of the patients in the abciximab group (110 patients) and in 13.4% in the bivalirudin group (115 patients) (relative risk, 0.96; 95% CI, 0.74 to 1.25; P=0.76). Major bleeding occurred in 4.6% of the patients in the abciximab group (40 patients) as compared with 2.6% in the bivalirudin group (22 patients) (relative risk, 1.84; 95% CI, 1.10 to 3.07; P=0.02).
Abciximab and unfractionated heparin, as compared with bivalirudin, failed to reduce the rate of the primary end point and increased the risk of bleeding among patients with non-ST-segment elevation myocardial infarction who were undergoing PCI. (Funded by Nycomed Pharma and others; ISAR-REACT 4 ClinicalTrials.gov number, NCT00373451.).
Objectives This study sought to compare the safety and efficacy of the zotarolimus-eluting stent (ZES) and the everolimus-eluting stent (EES) for treatment of unprotected left main coronary artery ...(uLMCA) disease. Background The second-generation ZES and EES have reduced the risk of restenosis in large patient cohorts. However, their comparative performance in uLMCA lesions is not known. Methods In this study, patients with symptomatic coronary artery disease undergoing percutaneous coronary intervention for uLMCA lesions were randomly assigned to receive either a ZES (n = 324) or an EES (n = 326). The primary endpoint was the combined incidence of death, myocardial infarction, and target lesion revascularization at 1 year. Secondary endpoints were definite or probable stent thrombosis at 1 year and angiographic restenosis based on analysis of the left main coronary artery area at follow-up angiography. Results At 1 year, the cumulative incidence of the primary endpoint was 17.5% in the ZES group and 14.3% in the EES group (relative risk: 1.26; 95% confidence interval CI: 0.85 to 1.85; p = 0.25). Three patients in the ZES group (0.9%) and 2 patients in the EES group (0.6%) experienced definite or probable stent thrombosis (p > 0.99). All-cause mortality at 1 year was equal in the 2 groups (5.6%; relative risk: 1.00; 95% CI: 0.52 to 1.93; p = 0.98). Angiographic restenosis occurred in 21.5% of patients in the ZES group and 16.8% in the EES group (relative risk: 1.28; 95% CI: 0.86 to 1.92; p = 0.24). Conclusions Within the statistical limitations of the present study, treatment of uLMCA lesions with a ZES or an EES provided comparable clinical and angiographic outcomes at 1-year follow-up. (Intracoronary Stenting and Angiographic Results: Drug-Eluting Stents for Unprotected Coronary Left Main Lesions ISAR-LEFT MAIN-2; NCT00598637 )
Background High-sensitivity cardiac troponin assays enable the measurement of cardiac troponin concentrations in the majority of patients with coronary artery disease. The objective of this study was ...to investigate the prognostic value of sensitive cardiac troponin in patients with stable and unstable angina presenting with undetectable levels of conventional troponin. Methods This study included 1,057 patients with stable (808 patients) or unstable (249 patients) angina who presented with undetectable conventional cardiac troponin T and underwent coronary artery revascularization. The cardiac troponin T was measured with conventional and high-sensitivity assays, in parallel, using the same plasma sample. The primary end point was 4-year mortality. Results The total sensitive troponin T level (median interquartile range) was 0.008 (0.005-0.014) μg/L. Variables independently associated with an elevated level of sensitive troponin T were elderly age, male sex, higher body mass index, presence of diabetes, unstable angina, increased New York Heart Association class, reduced left ventricular ejection fraction, elevated level of N-terminal pro-brain natriuretic peptide, reduced glomerular filtration rate, and elevated level of C-reactive protein. During the follow-up period, there were 83 deaths. The sensitive troponin T level was an independent predictor of 4-year mortality (adjusted hazard ratio = 1.47 with 95% CI 1.17-1.84, P < .001 for each unit increase in the natural logarithm of the sensitive troponin T). Conclusions The elevated levels of sensitive cardiac troponin T in patients with stable or unstable angina presenting with undetectable conventional cardiac troponin T are significantly associated with reduced survival.
The crystal orientation fabric (COF) in ice cores provides detailed information, such as grain size and distribution and the orientation of the crystals in relation to the large-scale glacier flow. ...These data are relevant for a profound understanding of the dynamics and deformation history of glaciers and ice sheets. The intrinsic, mechanical anisotropy of the ice crystals causes an anisotropy of the polycrystalline ice of glaciers and affects the velocity of acoustic waves propagating through the ice. Here, we employ such acoustic waves to obtain the seismic anisotropy of ice core samples and compare the results with calculated acoustic velocities derived from COF analyses. These samples originate from an ice core from Rhonegletscher (Rhone Glacier), a temperate glacier in the Swiss Alps. Point-contact transducers transmit ultrasonic P waves with a dominant frequency of 1 MHz into the ice core samples and measure variations in the travel times of these waves for a set of azimuthal angles. In addition, the elasticity tensor is obtained from laboratory-measured COF, and we calculate the associated seismic velocities. We compare these COF-derived velocity profiles with the measured ultrasonic profiles. Especially in the presence of large ice grains, these two methods show significantly different velocities since the ultrasonic measurements examine a limited volume of the ice core, whereas the COF-derived velocities are integrated over larger parts of the core. This discrepancy between the ultrasonic and COF-derived profiles decreases with an increasing number of grains that are available within the sampling volume, and both methods provide consistent results in the presence of a similar amount of grains. We also explore the limitations of ultrasonic measurements and provide suggestions for improving their results. These ultrasonic measurements could be employed continuously along the ice cores. They are suitable to support the COF analyses by bridging the gaps between discrete measurements since these ultrasonic measurements can be acquired within minutes and do not require an extensive preparation of ice samples when using point-contact transducers.
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