Motivation of patients with inflammatory bowel disease to participate in a clinical trial.

Background: Clinical trials are designed to investigate innovative diagnostic and therapeutic strategies for patients. However, factors that influence patients with inflammatory bowel disease (IBD) and willingness to participate in a clinical trial are unknown. Methods: We developed a questionnaire and asked IBD patients about their willingness to hypothetically participate in a clinical trial and their current health-related quality of life by using the IBDQ. Results: Of 201 distributed questionnaires, 166 were returned and included in the analysis. One-hundred-one (61 %) patients declared their willingness to participate in a clinical trial hypothetically offered in their current situation, whereas 65 (39 %) declined. Among all patients, a trustful relationship between patient and doctor was most important for trial participation. The willingness to help others and to support medical progress were other key issues mentioned. In contrast, those patients inclined to refuse trial participation feared impairment of their current health status, potential side effects, medical examinations, and the expenditure of time and effort. Conclusion: In our cohort of IBD patients, approximately two-thirds were willing to participate in a clinical trial. We were able to identify a number of factors that should help physicians to directly address fears and break down barriers in order to increase the number of patients willing to participate in clinical trials.

[Rational and efficient diagnosis in different stages of Crohn's disease]. / Rationale und rationelle Diagnostik in unterschiedlichen Krankheitsphasen des Morbus Crohn.

The treatment of patients with inflammatory bowel disease has become more complex in recent years through the introduction of various immunosuppressive agents as well as the approval of monoclonal antibodies. Patients receiving such treatment must be carefully monitored. National and international guidelines define a diagnostic and therapeutic context for the practitioner, but can only partially respond to specific questions on the procedure for individual patients. Within the framework of a project initiated by Abbott entitled "IBD ahead" 34 German IBD experts have elaborated concrete proposals for the utility of clinical symptom assessment, endoscopy and the use of laboratory parameters including foecal markers of inflammation. Furthermore, we discuss the significance of conventional X-rays, computed tomography, ultrasound and magnetic resonance tomography. These recommendations are illustrated by case studies from everyday practice in the participating centres.

[IBD ahead 2010--Answering important questions in Crohn's disease treatment]. / IBD ahead 2010--Antworten auf zehn zentrale Fragen in der aktuellen Therapie des Morbus Crohn.

The treatment of patients with inflammatory bowel disease has become more complex in recent years through the introduction of various immunosuppressive agents as well as the approval of monoclonal antibodies against TNF-α and patients receiving such treatment must be carefully monitored. National and international guidelines define a diagnostic and therapeutic context for the practitioner, but can only partially respond to specific questions on the procedure for individual patients. Within the framework of a project initiated by Abbott entitled "IBD ahead" 38 German IBD experts have elaborated concrete proposals for dealing with corticosteroids, immunosuppressants and TNF-α antibodies on the basis of the published literature and their own personal experience in order to close the gap between these guidelines and daily clinical practice. Statements were developed on the choice of correct timing of initiation, dose and duration of the individual substances and on how to proceed with patients exhibiting treatment failure. Moreover, recommendations are also made on drug combination strategies, safety monitoring and the risks regarding the development of infectious complications and malignancies. These recommendations are illustrated by case studies from everyday practice in participating centres.

Expression of resistance to Friend virus-stimulated erythropoiesis in bone marrow chimeras containing Fv-2rr and Fv-2ss bone marrow.

Bone marrow chimeras were formed containing mixtures of DBA/2 (Fv-2ss, Hbbdd) and B10.D2 (Fv-2rr, Hbbss) bone marrow. When these mice were infected with the polycythemia-inducing strain of Friend virus, erythropoiesis was stimulated, but the proportion of B10.D2 hemoglobin fell rapidly and newly synthesized hemoglobin was essentially all of the DBA/2 type. The treatment of infected polycythemic chimeras with phenylhydrazine lowered the hematocrit and restored the synthesis of B10.D2 hemoglobin. These results imply that B10.D2 erythroid precursors are intrinsically resistant to Friend virus-stimulated erythropoiesis. The experiments also suggest that virus-stimulated erythropoiesis is not mediated by a factor or cell-cell interactions, unless such factors or interactions do not act across strain barriers.

Safety of glucose-containing solutions during accidental hyperinfusion in piglets.

BACKGROUND: Errors in fluid management can lead to significant morbidity in children. We conducted an experimental animal study to determine the margin of safety in accidental hyperinfusion of different glucose and electrolyte containing solutions. METHODS: Fifteen piglets [bodyweight 12.1 (sd 2.0) kg] were randomly assigned to receive either 100 ml kg⁻¹ of balanced electrolyte solution with glucose 1% (BS-G1), hypotonic electrolyte solution with glucose 5% (HE-G5), or glucose 40% solution (G40) over 1 h. Blood electrolytes, glucose, and osmolality and intracranial pressure (ICP) were measured before, during, and after fluid administration. RESULTS: Hyperinfusion of BS-G1 led to moderate hyperglycaemia [baseline 3.4 (sd 1.3) mmol litre⁻¹, study end 12.6 (1.8) mmol litre⁻¹], but no other relevant pathophysiological alterations. Hyperinfusion of HE-G5 produced marked hyperglycaemia [baseline 3.9 (1.2) mmol litre⁻¹, study end 48.6 (4.3) mmol litre⁻¹, P < 0.05] and hyponatraemia [baseline 136.4 (1.3) mmol litre(-1), study end 119.6 (2.1) mmol litre⁻¹, P < 0.05], whereas osmolality remained stable during the course of the study. Hyperinfusion of G40 induced acute hyperglycaemic/hyperosmolar decompensation with an extreme decrease in serum electrolytes [e.g. sodium baseline 138 (1.1) mmol litre⁻¹, 30 min 87.8 (6.4) mmol litre⁻¹, P < 0.01], leading to cardiac arrest after infusion of 50-75 ml kg⁻¹. ICP remained within a physiological range in all groups. CONCLUSIONS: In an animal model of accidental hyperinfusion, BS-G1 showed the widest margin of safety and can therefore be expected to enhance patient safety in perioperative fluid management in children; HE-G5 proved significantly less safe; and G40 was found to be outright hazardous.

Inflammatory Bowel Disease in the COVID-19 Pandemic: the Patients' Perspective.

BACKGROUND: The coronavirus disease 2019 [COVID-19] pandemic is affecting lives worldwide. The influence of inflammatory bowel disease [IBD] medication and IBD itself on COVID-19 is controversial. Additionally, IBD-focused guidance is scarce. OBJECTIVE: Our aims were to determine COVID-19 prevalence/exposure, perception and information sources, medication compliance, patient behaviour and physician contact among patients with IBD compared with non-IBD controls. METHODS: A cross-sectional anonymous survey of patients with IBD [N = 415] at one university IBD clinic and one gastroenterology practice, matched 4:1 with control participants [N = 116], was performed. RESULTS: Patients with IBD had a high fear of infection. This was more pronounced in patients taking immunosuppressants and it extended to hospitals, private practices and public places, such as supermarkets. IBD patients reported leaving their homes less frequently than their peers without IBD. A total of 90% of patients with IBD reported washing their hands more frequently. Patients taking immunosuppressants were concerned about interactions between medication and COVID-19, whereas patients taking 5-aminosalicylates were not. Nonetheless, 96.4% of patients adhered to continuing their medication. Patients sought guidance primarily from television and internet news sites. Video consultations were found to be a suitable solution for a subset of patients who are young, have a high level of fear and leave their home less frequently than their peers, whereas overall acceptance of video consultations was limited. CONCLUSION: Patients with IBD are significantly more affected by the COVID-19 pandemic than their non-IBD peers, but they continue to adhere to their medication regimens. IBD-focused COVID-19 information should be actively conveyed.

Murine leukemia virus: high-frequency activation in vitro by 5-iododeoxyuridine and 5-bromodeoxyuridine.

Cells of embryos of the high leukemic mouse strain AKR can be grown in culture as virus-negative cell lines. However, these lines and clonal sublines uniformly have the capacity to initiate synthesis of murine leukemia virus. Exposure of the cells to 5-iododeoxyuridine or 5-bromodeoxyuridine induced synthesis of virus in as high as 0.1 to 0.5 percent of the cells; many of the cells were producing virus as soon as 3 days after initiation of treatment. Induction of virus by these drugs is several orders of magnitude greater than that obtained with any other treatment tested. These studies indicate that the full genome of murine leukemia virus is present in an unexpressed form in all AKR cells and provide a potentially powerful technique for activating leukemia virus genomes in other cell systems.

[Prevention of gastrointestinal malignancies]. / Prävention von Malignomen des Verdauungstrakts.

Malignancies of the gastrointestinal tract are the most common causes of cancer-related deaths in Germany. They also induce significant morbidity. Despite both surgical and medical therapeutic improvements, advanced stages of these cancers can rarely be cured. Preventive and screening measures are suitable to decrease gastrointestinal cancer-related mortality. Weight reduction and cessation of smoking are effective in preventing esophageal, pancreatic and colorectal cancer. Treatment of infections like chronic viral hepatitis and helicobacter pylori gastritis is able to protect from hepatocellular and gastric cancer, respectively. Colonoscopy is one of the best established screening methods. It allows early detection of colorectal neoplasia. Preneoplastic adenomas can be endoscopically removed during the same session. We here review simple prevention strategies and effective screening methods in gastrointestinal cancers of relevance in daily practice.

Vedolizumab in the treatment of chronic, antibiotic-dependent or refractory pouchitis.

BACKGROUND: The most common complication after ileal pouch anal anastomosis in up to 50% of patients is an acute pouchitis. The majority of patients respond to antibiotic treatment. However, 10%-15% develops chronic antibiotic-dependent or refractory pouchitis which is usually hard to treat. AIM: To evaluate the effectiveness of vedolizumab in patients with chronic pouchitis. METHODS: Patients with chronic antibiotic-dependent or refractory pouchitis were treated with vedolizumab (300 mg at week 0, 2, 6 and 10) in 10 IBD centres and retrospectively registered. Data were recorded until week 14 of vedolizumab treatment. In total 20 patients (12 male, median age 43 years) were included for analysis. The effectiveness was measured using the Oresland Score (OS) at week 2, 6, 10 and 14 and the pouch disease activity index (PDAI) at week 0 and 14. RESULTS: The mean OS declined from 6.8 (range 2-12) to 3.4 (range 0-11). Concordantly, the mean PDAI after 14 weeks of treatment dropped from 10 (range 5-18) to 3 (range 0-10). Only three patients reported moderate side effects. No serious side effects were recorded. In addition, symptomatic co-medication such as loperamide and tincture of opium could be terminated in 8 out of 12 patients as well as antibiotic treatment could be stopped in 17 out of 19 patients. CONCLUSION: Our data indicate that vedolizumab could be an option in the treatment of patients with chronic, antibiotic-dependent or refractory pouchitis.

Microbial Spectrum of Intra-Abdominal Abscesses in Perforating Crohn's Disease: Results from a Prospective German Registry.

BACKGROUND: Intra-abdominal abscesses [IAAs] are common life-threatening complications in patients with Crohn's disease [CD]. In addition to interventional drainage and surgical therapy, empirical antibiotic therapy represents a cornerstone of treatment, but contemporary data on microbial spectra and antimicrobial resistance are scarce. METHODS: We recruited 105 patients with CD and IAAs from nine German centres for a prospective registry in order to characterize the microbiological spectrum, resistance profiles, antibiotic therapy and outcome. RESULTS: In 92 of 105 patients, microbial investigations of abscess material revealed pathogenic microorganisms. A total of 174 pathogens were isolated, with a median of 2 pathogens per culture [range: 1-6]. Most frequently isolated pathogens were E. coli [45 patients], Streptococcus spp. [28 patients], Enterococci [27 patients], Candida [13 patients] and anaerobes [12 patients]. Resistance to third-generation cephalosporins, penicillins with beta-lactamase inhibitors and quinolones were observed in 51, 36 and 35 patients, respectively. Seven patients had multiple-drug-resistant bacteria. Thirty patients received inadequate empirical treatment, and this was more frequent in patients receiving steroids or immunosuppression [37%] than in patients without immunosuppression [10%: p = 0.001] and was associated with a longer hospital stay [21 days vs 13 days, p = 0.003]. CONCLUSION: Based on antimicrobial resistance profiles, we herein report a high rate of inadequate empirical first-line therapy for IAAs in CD, especially in patients receiving immunosuppression, and this is associated with prolonged hospitalization.

Postnatal development of alveoli. Regulation and evidence for a critical period in rats.

In many species, including humans, pulmonary alveoli are formed after birth by septal subdivision of the large gas-exchange saccules present at birth. In rats septation occurs mainly between the 4th and 14th postnatal days (Burri, P. H. 1974. Anat. Rec. 180:77-98), but little is known about the regulation of this process. We found that dexamethasone (0.1 micrograms daily) given to rats from age 4 to 13 d markedly impaired saccule septation to at least age 60 d and also diminished the extent of the increase of alveolar surface area (Sa). Underfeeding from birth to age 14 d did not diminish saccule septation but did result in diminished Sa. We conclude dexamethasone-treated rats have a critical period during which the gas-exchange saccules present at birth must be subdivided. Since Sa increased in dexamethasone-treated rats without a change in alveolar size, and, the enlargement of Sa was diminished in underfed rat pups without a deficit of saccule septation, we postulate new alveoli were formed by means other than septation of the large gas-exchange saccules present at birth. Furthermore, these various means of forming alveoli, and hence of increasing Sa, were differently regulated: dexamethasone decreased the enlargement of Sa brought about by both septation of the gas-exchange saccules present at birth and by other, as yet unidentified, means of forming alveoli; underfeeding did not diminish Sa increases produced by saccule septation but did decrease the extent of Sa enlargement due to the other means of forming alveoli.

Neurologic manifestations of ulcerative colitis.

Ulcerative colitis (UC) has traditionally been considered to be an inflammatory disease limited to the colonic mucosa. However, since it has been shown that UC is frequently accompanied by various extraintestinal disorders, there is increasing evidence that UC may also manifest in the nervous system. The following review focuses particularly on these possible manifestations of UC, both in the peripheral (PNS), and in the central nervous system (CNS). A systematic literature search according to the MEDLINE database was performed for this purpose. Although a reliable differentiation may clinically not always be possible, three major pathogenic entities can be differentiated: (i) cerebrovascular disease as a consequence of thrombosis and thromboembolism; (ii) systemic and cerebral vasculitis; (iii) probably immune mediated neuropathy and cerebral demyelination. With the exception of thromboembolism and sensorineural hearing loss, evidence for a causal relationship relies merely on single case reports or retrospective case series. Considering the CNS-manifestations, similarities between UC-associated disorders of the white matter and acute disseminated encephalomyelitis (ADEM) are obvious. Epileptic seizures, unspecified encephalopathies and confusional states are most likely epiphenomena that have to be regarded symptomatic rather than as own entities. A prospective study on the neurologic aspects of UC would be very welcome.

[How does the ileoanal pouch keep its promises? : Functioning of the ileoanal pouch after restorative proctocolectomy]. / Wie hält der ileoanale Pouch was er verspricht? : Die Funktion des ileoanalen Pouches nach restaurativer Proktokolektomie.

Restorative proctocolectomy with an ileoanal pouch anastomosis (IAPA) is the surgical therapy of choice for patients with refractory ulcerative colitis and/or associated (pre)neoplastic lesions. It is predominantly performed laparoscopically. Reconstruction with a J­pouch is the most frequently applied variant due to the ideal combination of technical simplicity and good long-term results. In the present review, potential postoperative pouch complications, their risk factors, diagnostics and surgical management, as well as mid-term and long-term quality of life after pouch construction are differentially presented based on the current literature.

[Laparoscopic proctocolectomy technique : Restorative proctocolectomy with ileal pouch-anal anastomosis in ulcerative colitis. Video article]. / Technik der laparoskopischen Proktokolektomie : Restaurative Proktokolektomie mit ileopouchanaler Anastomose bei Colitis ulcerosa. Videobeitrag.

Laparoscopic restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) constitutes a curative treatment option for therapy-refractory ulcerative colitis. A two-stage procedure with loop ileostomy at the time of IPAA is the most frequent variant of surgery. The aim of the procedure is the complete removal of the colon and rectum with simultaneous restoration of gastrointestinal continuity and preservation of continence functions. Long-term quality of life following laparoscopic proctocolectomy with IPAA is good and comparable with a healthy reference population. The surgical technique is demonstrated in detail with the help of a video of the operation, which is available online.