Eosinophilic gastroenteritis with refractory ulcer disease and gastrointestinal bleeding as a rare manifestation of seronegative gastrointestinal food allergy

Gastrointestinal bleeding and iron deficiency anaemia may cause severe symptoms and may require extensive diagnostics and substantial amounts of health resources. This case report focuses on the clinical presentation of a 22 year old patient with recurrent gastrointestinal bleeding from multilocular non-healing ulcers of the stomach, duodenum and jejunum over a period of four years. Extensive gastroenterological and allergological standard diagnostic procedures showed benign ulcerative lesions with tissue eosinophilia, but no conclusive diagnosis. Multiple diagnostic procedures were performed, until finally, endoscopically guided segmental gut lavage identified locally produced, intestinal IgE antibodies by fluoro-enzyme-immunoassay. IgE antibody concentrations at the intestinal level were found to be more-fold increased for total IgE and food-specific IgE against nuts, rye flour, wheat flour, pork, beef and egg yolk compared with healthy controls. Thus, a diet eliminating these allergens was introduced along with antihistamines and administration of a hypoallergenic formula, which resulted in complete healing of the multilocular ulcers with resolution of gastrointestinal bleeding. All gastrointestinal lesions disappeared and total serum IgE levels dropped to normal within 9 months. The patient has been in remission now for more than two years. Eosinophilic gastroenteritis (EG) is well known to induce refractory ulcer disease. In this case, the mechanisms for intestinal damage and gastrointestinal bleeding were identified as local gastrointestinal type I allergy. Therefore, future diagnostics in EG should also be focused on the intestinal level as identification of causative food-specific IgE antibodies proved to be effective to induce remission in this patient

Brown bowel syndrome: A rare complication in diseases associated with long-standing malabsorption

BACKGROUND/AIMS Longtime chronic malabsorption may among other things cause a lack of liposoluble vitamins. Vitamin E deficiency can lead to formation of lipofuscin aggregates. Its deficiency is also associated with an increased lipofuscinosis of the bowel, i.e. brown bowel syndrome. METHODS Systematic research via Medline on brown bowel syndrome, lipofuscinosis, and vitamin E deficiency was performed. We combined our own clinical experience and a review of the literature for this paper. Its goal is to inform about the possible consequences of severe malabsorption and brown bowel syndrome. RESULTS Systematic data about the occurrence of severe malabsorption and brown bowel syndrome are rare. Only about 27 scientific reports can be found on this subject. Brown bowel syndrome is found mostly in conjunction with vitamin E deficiency and lipofuscinosis of the bowel. The clinical findings are caused by both malabsorption and lipofuscinosis. Case reports show a therapeutic effect of vitamin E. CONCLUSION Vitamin deficiency caused by longtime chronic malabsorption can lead to the development of brown bowel syndrome, which is seen as the expression of lipofuscinosis of the bowel, and can cause further clinical disorders. Patients with malabsorption should therefore be monitored regarding their vitamin E levels

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Service Systems in Changing Paradigms: An Inquiry Through the Systems Sciences

For professionals at the beginning of the 21st century, much of the conventional wisdom on business management and engineering is founded in the 20th century industrial / manufacturing paradigm. In developed economies, however, the service sector now dominates the manufacturing sector, just as manufacturing prevailed over the agricultural sector after the industrial revolution.\ud This chapter proposes the development of a body of knowledge on services systems, based on foundations in the systems sciences. The approach includes the design of\ud the systems of inquiry, acknowledging that body of knowledge on 21st century service systems is relatively nascent. A program of action science is proposed, with an\ud emphasis on multiple realities and knowledge development through dialectic. The outcome pursued is an increased number of T-shaped people with depth and breadth\ud in service systems, in communities of inquiry of researchers and practitioners

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Detection of right ventricular infarction using cardiovascular magnetic resonance imaging

Hintergrund und Ziele Ein Myokardinfarkt der Hinterwand geht in bis zu 50% der Fälle mit einem Infarkt des rechten Ventrikels einher. Aufgrund seiner speziellen Pathophysiologie erfordert der rechtsventrikuläre Infarkt einen anderen Therapieansatz als der singuläre linksventrikuläre Infarkt und weist zudem eine deutlich schlechtere Prognose auf. Limitationen der herkömmlichen diagnostischen Verfahren wie Elektrokardiogramm (EKG) und Echokardiographie lassen rechtsventrikuläre Infarkte in der Akutdiagnostik oft übersehen. Mittels Kontrastmittelverstärkter Magnetresonanztomographie (ceMRT) kann man einen linksventrikulären Infarkt zuverlässig und nicht-invasiv diagnostizieren. Zielsetzung dieser Arbeit war es, die Möglichkeit der kardialen MRT sowohl in der Spätphase als auch der Turbo-Inversion-Recovery-Magnitude-Sequenz (TIRM) hinsichtlich der Detektion eines rechtsventrikulären Infarktes zu evaluieren. Methoden Fünfundzwanzig Patienten mit akutem Hinterwandinfarkt wurden in diese Studie eingeschlossen. Um einen rechtsventrikulären Infarkt auszuschließen oder nachzuweisen wurde ein EKG, inklusive rechtsseitigen Ableitungen, geschrieben sowie eine Echokardiographie durchgeführt. Nach Revaskularisierung der Koronararterien mittels Herzkatheteruntersuchung (HKU) wurde eine ceMRT in der Spätphase als auch in der TIRM Sequenz durchgeführt. Hierbei wurde das Vorhandensein eines rechtsventrikulären Infarktes bestätigt oder ausgeschlossen und dessen Ausmaß quantifiziert. Ergebnisse Bei 13 der 25 (52%) Patienten zeigte sich in der Spätphase ein rechtsventrikulärer Infarkt. Bei 10 dieser Patienten war eine ST-Streckenerhöhung um mindestens 0,1mV in rV4 verzeichnet (Kappa 0,6815, p 0,0003). In der Echokardiographie wurde nur bei 5 Patienten der Verdacht auf einen rechtsventrikulären Infarkt geäußert (Kappa 0,1418 p 0,2345). In der TIRM Sequenz zeigte sich lediglich bei 6 Patienten ein rechtsventrikulärer Infarkt, bei allen wurde diese Diagnose bereits in der Spätphase gestellt (Kappa 0,451 p 0,0035). Zusätzlich wurden die Infarkte in der MRT quantifiziert. In der Spätphase stellten sich 9 Infarkte als groß dar, 4 als klein. Die 6 Infarkte die sich in der TIRM Sequenz demaskierten unterteilten sich in 4 Große und 2 kleine, wobei alle zuvor in der Spätphase als groß beschrieben worden waren. Schlussfolgerung Der Nachweis eines rechtsventrikulären Infarktes gelingt in der Spätphase der MRT zuverlässiger als mit den bisherigen, standardmäßig durchgeführten Untersuchungen (EKG und Echokardiographie). Auch ist eine Quantifizierung hinsichtlich der Infarktgröße möglich. Der Nachweis mittels TIRM Sequenz hingegen gelingt deutlich seltener und nur bei größere, infarzierten Arealen, so dass sich hier keine Alternative zur Spätphase ergibt.Background: About every other inferior wall infarction is accompanied by right ventricular infarction. Due to a different physiology, the right ventricular infarction requires a special treatment as compared to the sole leftventricular infarction of the inferior wall. Furthermore rightventricular infarction is associated with a more unfavorable prognosis. Due to limitations of the different diagnostic tools like Electrocardiogram (ECG) and Echocardiogram the accuracy to detect right ventricular infarction lacks. Using late enhancemement cardiovascular magnetic resonance imaging (LE CMR) left ventricular infarction can be accurately detected. Thus, the aim of this study was to evaluate the capability for detection of right ventricular infarction in inferior wall infarction using LE CMR and also to evaluate herefore another sequence, the Turbo-Inversion-Recovery-Magnitude-Sequence (TIRM). Methods: Twentyfive patients with acute inferior wall infarction were included in this study. To test for right ventricular infarction, patients underwent ECG, including right precordial leads, and an echocardiogram after admittance were obtained. After coronary reperfusion CMR was performed, obtaining results of LE CMR and TIRM sequences. In patients with right ventricular infarction, the size was measured and the infarction quantified as big or small infarction. Results: LE CMR detected in 13 of 25 (52%) patients a right ventricular infarction. 10 of these patients also showed a ST elevation of at least 0,1mV in rV4 (Kappa 0,6815, p 0,0003). In echocardiogram only 5 (Kappa 0,1418 p 0,2345) and using TIRM 6 right ventricular infarctions (Kappa 0,451 p 0,0035) were discovered. Furthermore the size of the infarctions were quantified using CMR. In LE CMR 9 infarctions were classified as large, 4 as small, whilst in the TIRM sequence 6 out of those 9 large infarction were discovered, quantifying 4 as large and 2 as small. None of the small infarctions in LE CMR were discovered using TIRM. Conclusions: Using LE CMR, right ventricular infarction in patients with inferior wall infarction is more frequently detected than with other routine diagnostics, such as ECG and Echocardiogram. Furthermore an accurate description concerning infarction size can be made using LE CMR. Detection of the infarction using TIRM is less accurate and furthermore the size of the infarction is underestimated

Intravenous vitamin C in the treatment of allergies: an interim subgroup analysis of a long-term observational study

Objective Oxidative stress appears to be a key factor in the pathogenesis of allergic diseases and a potential therapeutic target in allergy treatment. Allergic diseases are reportedly associated with reduced plasma levels of ascorbate, which is a key physiological antioxidant. Ascorbate prevents excessive inflammation without reducing the defensive capacity of the immune system. Methods An interim analysis of a multicenter, prospective, observational study was conducted to investigate the change in disease-specific and nonspecific symptoms (fatigue, sleep disorders, depression, and lack of mental concentration) during adjuvant treatment with intravenous vitamin C (Pascorbin®; Pascoe, Giessen, Germany) in 71 patients with allergy-related respiratory or cutaneous indications. Results Between the start and end of treatment, the mean sum score of three disease-specific symptoms decreased significantly by 4.71 points and that of four nonspecific symptoms decreased significantly by 4.84 points. More than 50% of patients took no other allergy-related medication besides vitamin C. Conclusions Our observations suggest that treatment with intravenous high-dose vitamin C reduces allergy-related symptoms. Our observations form a basis for planning a randomized controlled clinical trial to obtain more definitive evidence of the clinical relevance of our findings. We also obtained evidence of ascorbate deficiency in allergy-related diseases

Plasma concentrations of ascorbic acid in a cross section of the German population

Objectives Vitamin C deficiency is considered extremely rare in modern industrialized countries. This study was performed to assess vitamin C concentrations in the German population. Methods As part of a consultant–patient seminar on nutrition and food intolerances, patients were asked to participate in this study on a voluntary basis. Blood samples were taken for analysis of serum vitamin C concentrations, and all patients were asked to complete a questionnaire. The vitamin C concentration was determined by high-performance liquid chromatography. Results Of approximately 300 patients attending the seminar, 188 (62.6%) consented to vitamin C blood sample analysis and 178 (59.3%) answered the questionnaire. The mean vitamin C concentration was 7.98 mg/L (range, 0.50–17.40; reference range, 5–15 mg/L). A low plasma level with vitamin C insufficiency (<5 mg/L) was found in 31 patients (17.4%), and a potential scorbutogenic deficiency (<1.5 mg/L) was found in 6 (3.3%). Conclusions Potential vitamin C insufficiency and deficiency is common. It is therefore possible, even in modern developed populations, that certain individuals may require a higher intake of vitamin C

Colon Capsule Endoscopy: Detection of Colonic Polyps Compared with Conventional Colonoscopy and Visualization of Extracolonic Pathologies

BACKGROUND: Conventional colonoscopy (CC) is the gold standard for diagnostic examination of the colon. However, the overall acceptance of this procedure is low due to patient fears of complications or embarrassment. Colon capsule endoscopy (CCE) represents a minimally invasive, patient-friendly procedure that offers complete visualization of the entire intestine