Jan C. Preiß

Impact of restless legs syndrome in patients with inflammatory bowel disease on sleep, fatigue, and quality of life

PurposeInflammatory bowel disease has been associated with neurological symptoms including restless legs syndrome. Here, we investigated the impact of restless legs syndrome in patients with inflammatory bowel disease on sleep, fatigue, mood, cognition, and quality of life.MethodsTwo groups of inflammatory bowel disease patients, with and without restless legs syndrome, were prospectively evaluated for sleep disorders, fatigue, daytime sleepiness, depression, anxiety, and health-related quality of life. Furthermore, global cognitive function, executive function, attention, and concentration were assessed in both groups. Disease activity and duration of inflammatory bowel disease as well as current medication were assessed by interview. Inflammatory bowel disease patients with and without restless legs syndrome were matched for age, education, severity, and duration of their inflammatory bowel disease.ResultsPatients with inflammatory bowel disease and clinically relevant restless leg syndrome suffered significantly more frequent from sleep disturbances including sleep latency and duration, more fatigue, and worse health-related quality of life as compared to inflammatory bowel disease patients without restless legs syndrome. Affect and cognitive function including cognitive flexibility, attention, and concentration showed no significant differences among groups, indicating to be not related to restless legs syndrome.ConclusionsSleep disorders including longer sleep latency, shorter sleep duration, and fatigue are characteristic symptoms of restless legs syndrome in inflammatory bowel disease patients, resulting in worse health-related quality of life. Therefore, clinicians treating patients with inflammatory bowel disease should be alert for restless legs syndrome.

Simultaneous Presence of Non- and Highly Mutated Keyhole Limpet Hemocyanin (KLH)-Specific Plasmablasts Early after Primary KLH Immunization Suggests Cross-Reactive Memory B Cell Activation

There are currently limited insights into the progression of human primary humoral immunity despite numerous studies in experimental models. In this study, we analyzed a primary and related secondary parenteral keyhole limpet hemocyanin (KLH) immunization in five human adults. The primary challenge elicited discordant KLH-specific serum and blood effector B cell responses (i.e., dominant serum KLH-specific IgG and IgM levels versus dominant KLH-specific IgA plasmablast frequencies). Single-cell IgH sequencing revealed early appearance of highly (>15 mutations) mutated circulating KLH-specific plasmablasts 2 wk after primary KLH immunization, with simultaneous KLH-specific plasmablasts carrying non- and low-mutated IgH sequences. The data suggest that the highly mutated cells might originate from cross-reactive memory B cells (mBCs) rather than from the naive B cell repertoire, consistent with previous reported mutation rates and the presence of KLH-reactive mBCs in naive vaccinees prior to immunization. Whereas upon secondary immunization, serum Ab response kinetics and plasmablast mutation loads suggested the exclusive reactivation of KLH-specific mBCs, we, however, detected only little clonal overlap between the peripheral KLH-specific secondary plasmablast IgH repertoire and the primary plasmablast and mBC repertoire, respectively. Our data provide novel mechanistic insights into human humoral immune responses and suggest that primary KLH immunization recruits both naive B cells and cross-reactive mBCs, whereas secondary challenge exclusively recruits from a memory repertoire, with little clonal overlap with the primary response.

Accuracy of diagnostic tests and a new algorithm for diagnosing cytomegalovirus colitis in inflammatory bowel diseases: a diagnostic study

PurposeThe optimal method for detecting CMV colitis in patients with inflammatory bowel disease (IBD) has not been established. We wanted to investigate which diagnostic test would be most accurate when defining CMV colitis rather by the further clinical course than by using another diagnostic modality.MethodsAll consecutive patients with moderately or severely active IBD who had been tested for CMV by PCR, histology, or antigenemia assay at the two campuses CBF and CCM of the Charité - Universitätsmedizin Berlin between September 2006 and September 2009 were included in this retrospective study. During that time, in patients with a positive CMV test, immunosuppressive treatment of any kind was immediately reduced and antiviral treatment was started. This allowed identifying patients who responded to antiviral treatment and those who only responded to later escalation of immunosuppressive therapy.ResultsOne hundred and nine patients were identified, out of whom nine were considered to have clinically relevant CMV colitis. Sensitivity and specificity were 1 and 0.94 for CMV PCR and 0.5 and 1 for pp65 antigen immunofluorescence assay from peripheral blood, 0.67 and 0.98 for immunohistochemistry, and 0.17 and 0.98 for hematoxylin-eosin staining. When using absence of leukocytosis, splenomegaly, and steroid refractory disease as clinical parameters to test for CMV colitis, blood CMV PCR and immunohistochemistry were able to exclude CMV colitis in negative patients with a 75% likelihood of positive patients to have clinically relevant CMV colitis.ConclusionsBlood-based CMV PCR together with simple clinical parameters can exclude clinically relevant CMV colitis at a high specificity.

Low Sensitivity of Simtomax Point of Care Test in Detection of Celiac Disease in a Prospective Multicenter Study

BACKGROUND & AIMS Point of care tests (POCTs) might be used to identify patients with undiagnosed celiac disease who require further evaluation. We performed a large multicenter study to determine the performance of a POCT for celiac disease and assessed celiac disease prevalence in endoscopy centers. METHODS We performed a prospective study of 1055 patients (888 adults; median age, 48 yrs and 167 children; median age, 10 yrs) referred to 8 endoscopy centers in Germany, for various indications, from January 2016 through June 2017. Patients were tested for celiac disease using Simtomax, which detects immunoglobulin (Ig)A and IgG antibodies against deamidated gliadin peptides (DGP). Results were compared with findings from histologic analyses of duodenal biopsies (reference standard). The primary aim was to determine the accuracy of this POCT for the detection of celiac disease, to identify candidates for duodenal biopsy. A secondary aim was to determine the prevalence of celiac disease in adult and pediatric populations referred for outpatient endoscopic evaluation. RESULTS The overall prevalence of celiac disease was 4.1%. The POCT identified individuals with celiac disease with 79% sensitivity (95% CI, 64%-89%) and 94% specificity (95% CI, 93%-96%). Positive and negative predictive values were 37% and 99%. When we analyzed the adult and pediatric populations separately, we found the test to identify adults with celiac disease (prevalence 1.2%) with 100% sensitivity and 95% specificity. In the pediatric population (celiac disease prevalence 19.6%), the test produced false-negative results for 9 cases; the test therefore identified children with celiac disease with 72% sensitivity (95% CI 53%-86%). Analyses of serologic data revealed significantly lower DGP titers in the false-negative vs the true-positive group. CONCLUSIONS In a study of more than 1000 adults and children, we found the Simtomax POCT to detect celiac disease with lower overall levels of sensitivity than expected. Although the test identifies adults with celiac disease with high levels of sensitivity and specificity, the prevalence of celiac disease was as low as 1.2% among adults. The tests lack of sensitivity might be due to the low intensity of the POCT bands and was associated with low serum DGP titers. Study ID no: DRKS00012499.

Calcified Liver Metastases from a Neuroendocrine Tumor of the Lung (Atypical Carcinoid) – A Case Report

Pulmonary neuroendocrine tumors (NETs) are rare tumors with an incidence rate of 0.2-2/100 000 population/year in Western countries (M. E. Caplin et al. Ann Oncol 2015; 26:1604-20). They account for 1-2% of all neoplasms of the lung and constitute one-fourth to one-third of all NETs. Atypical carcinoids are far less common than typical carcinoids and predominantly occur in male smokers aged 50 -70 years. Most pulmonary NETs are asymptomatic due to their peripheral location. Surgical resection is the treatment of choice. Medical management should take hormone-related symptoms into account.

Was ist gesichert in der Therapie chronisch entzündlicher Darmerkrankungen?@@@What has been confirmed in the treatment of inflammatory bowel disease?

ZusammenfassungDie Therapie chronisch entzündlicher Darmerkrankungen richtete sich bislang vorwiegend nach der Klinik: Bei fehlendem Ansprechen wurde die Therapie eskaliert, bis eine klinische Remission erreicht wurde. Die klinische Remission entspricht jedoch nicht einer mukosalen Abheilung. Analog zu den Daten zur rheumatoiden Arthritis zeigen vorliegende Studien, dass eine frühe effektive Behandlung chronisch entzündlicher Darmerkrankungen strukturelle Veränderungen reduzieren kann. In der vorliegenden Übersicht werden Arbeiten diskutiert, die die mukosale Abheilung als mögliches neues Therapieziel definieren. Die Identifikation von Risikofaktoren, die einen komplizierten Verlauf anzeigen, stellt einen ersten Schritt in Richtung einer individuellen Therapie chronisch entzündlicher Darmerkrankungen dar. Entsprechend soll auf Therapiestrategien und die dazugehörige Risikoabwägung eingegangen werden.AbstractThe therapy of inflammatory bowel diseases is currently guided by clinical variables. An escalation of immunosuppressive therapy is required in case of treatment failure. However, clinical remission does not necessarily imply mucosal healing. In parallel to the treatment of rheumatoid arthritis a novel concept is emerging suggesting that an early anti-inflammatory treatment can reduce structural changes in inflammatory bowel diseases. The studies supporting this novel therapeutic strategy that mucosal healing might build the future therapeutic goal will be discussed. In order to adjust the therapy, risk factors indicating a complicated disease course will be identified, resulting in the development of an individual disease course. The benefit of these strategies will be discussed together with therapy-associated complications.The therapy of inflammatory bowel diseases is currently guided by clinical variables. An escalation of immunosuppressive therapy is required in case of treatment failure. However, clinical remission does not necessarily imply mucosal healing. In parallel to the treatment of rheumatoid arthritis a novel concept is emerging suggesting that an early anti-inflammatory treatment can reduce structural changes in inflammatory bowel diseases. The studies supporting this novel therapeutic strategy that mucosal healing might build the future therapeutic goal will be discussed. In order to adjust the therapy, risk factors indicating a complicated disease course will be identified, resulting in the development of an individual disease course. The benefit of these strategies will be discussed together with therapy-associated complications.

Was ist gesichert in der Therapie chronisch entzündlicher Darmerkrankungen

ZusammenfassungDie Therapie chronisch entzündlicher Darmerkrankungen richtete sich bislang vorwiegend nach der Klinik: Bei fehlendem Ansprechen wurde die Therapie eskaliert, bis eine klinische Remission erreicht wurde. Die klinische Remission entspricht jedoch nicht einer mukosalen Abheilung. Analog zu den Daten zur rheumatoiden Arthritis zeigen vorliegende Studien, dass eine frühe effektive Behandlung chronisch entzündlicher Darmerkrankungen strukturelle Veränderungen reduzieren kann. In der vorliegenden Übersicht werden Arbeiten diskutiert, die die mukosale Abheilung als mögliches neues Therapieziel definieren. Die Identifikation von Risikofaktoren, die einen komplizierten Verlauf anzeigen, stellt einen ersten Schritt in Richtung einer individuellen Therapie chronisch entzündlicher Darmerkrankungen dar. Entsprechend soll auf Therapiestrategien und die dazugehörige Risikoabwägung eingegangen werden.AbstractThe therapy of inflammatory bowel diseases is currently guided by clinical variables. An escalation of immunosuppressive therapy is required in case of treatment failure. However, clinical remission does not necessarily imply mucosal healing. In parallel to the treatment of rheumatoid arthritis a novel concept is emerging suggesting that an early anti-inflammatory treatment can reduce structural changes in inflammatory bowel diseases. The studies supporting this novel therapeutic strategy that mucosal healing might build the future therapeutic goal will be discussed. In order to adjust the therapy, risk factors indicating a complicated disease course will be identified, resulting in the development of an individual disease course. The benefit of these strategies will be discussed together with therapy-associated complications.The therapy of inflammatory bowel diseases is currently guided by clinical variables. An escalation of immunosuppressive therapy is required in case of treatment failure. However, clinical remission does not necessarily imply mucosal healing. In parallel to the treatment of rheumatoid arthritis a novel concept is emerging suggesting that an early anti-inflammatory treatment can reduce structural changes in inflammatory bowel diseases. The studies supporting this novel therapeutic strategy that mucosal healing might build the future therapeutic goal will be discussed. In order to adjust the therapy, risk factors indicating a complicated disease course will be identified, resulting in the development of an individual disease course. The benefit of these strategies will be discussed together with therapy-associated complications.

Kurzfassung der aktualisierten S3-Leitlinie der Deutschen Gesellschaft für Verdauungs- und Stoffwechselkrankheiten (DGVS) und des Kompetenznetzes Darmerkrankungen zur Diagnostik und Behandlung des Morbus Crohn

Der Morbus Crohn gehört zu den häufigsten chronisch entzündlichen Erkrankungen des Gastrointestinaltrakts. Leitsymptome sind Durchfall, Bauchschmerzen und systemische Beschwerden wie Fieber und Gewichtsverlust. Neben Anamnese, klinischem Befund und Labordiagnostik kommt der Sonographie eine besondere Rolle bei Diagnosestellung und im Verlauf zu. Ergänzend muss zumindest initial und einmal im Verlauf eine Ileokoloskopie erfolgen. Die Therapie hängt von der Krankheitsaktivität und dem Befallsmuster ab. Schwere Schübe müssen mit systemischen Kortikosteroiden, leichte können mit topischen Steroiden behandelt werden. Bei langstreckigem Dünndarmbefall und/ oder Befall des oberen Gastrointestinaltrakts sollte großzügig die Indikation zur Immunsuppression gestellt werden, die sonst chronisch aktiven Verläufen vorbehalten ist. Das Immunsuppressivum erster Wahl ist Azathioprin/6-Mercaptopurin, Immunsuppressiva zweiter Wahl sind Methotrexat und Anti-TNF-α-Antikörper. Operationen kommen bei therapierefraktären Verläufen, Fisteln, langstreckigen Stenosen und bei lokalisiertem Befall in Betracht. Hochgradige Dysplasien oder Karzinome sind eine absolute Operationsindikation. Komplexe Verläufe erfordern die interdisziplinäre Behandlung durch den Gastroenterologen/gastroenterologisch spezialisierten Pädiater und den Viszeralchirurgen. Patienten müssen zu einer strikten Nikotinkarenz aufgefordert werden.

Leitlinie „Diagnostik und Therapie des Morbus Crohn“ – Kurzfassung für Internisten und Hausärzte

The German clinical practice guideline on diagnosis and therapy of Crohns disease is the result of an evidence-based consensus conference under the auspices of the German Gastroenterologic Society and the Competence Network IBD. This article will summarize the recommendations most important for the general practitioner.Crohns disease is diagnosed in cooperation with a gastroenterologist who is performing endoscopy and possibly ultrasound. Uncomplicated relapses can nevertheless be successfully treated at the office of a family physician - mostly with steroids. Steroids are not appropriate for long-term treatment though. In those cases an early treatment with immunosuppressants in collaboration with a gastroenterologist is required. Cooperation with several different sub specialists is necessary when surgery is required as well as for the treatment of fistula, psychosomatic aspects and extraintestinal manifestations.ZusammenfassungDie Leitlinie „Diagnostik und Therapie des Morbus Crohn“ ist das Ergebnis einer evidenzbasierten Konsensuskonferenz, die von der Deutschen Gesellschaft für Verdauungs- und Stoffwechselkrankheiten zusammen mit dem Kompetenznetz Chronisch entzündliche Darmerkrankungen ausgerichtet wurde. Hier sollen die für die praktische Arbeit von Internisten und Hausärzten wesentlichen Empfehlungen zusammengetragen werden.Während die initiale Diagnostik wegen der apparativen Untersuchungen die Zusammenarbeit mit einem endoskopierenden Kollegen erfordert, kann der unkomplizierte Schub in der hausärzlichen Praxis zumeist mit Steroiden erfolgreich behandelt werden. Für die Langzeittherapie sind Steroide aber ungeeignet. Hier sollte rechtzeitig eine Therapie mit Immunsuppressiva in Zusammenarbeit mit einem Gastroenterologen erfolgen. Bei notwendigen Operationen, der Therapie von Fisteln, psychosomatischen Aspekten und extraintestinalen Manifestationen ist die Zusammenarbeit mit Fachärzten verschiedener anderer Disziplinen notwendig.AbstractThe German clinical practice guideline on diagnosis and therapy of Crohn’s disease is the result of an evidence-based consensus conference under the auspices of the German Gastroenterologic Society and the Competence Network IBD. This article will summarize the recommendations most important for the general practitioner.Crohn’s disease is diagnosed in cooperation with a gastroenterologist who is performing endoscopy and possibly ultrasound. Uncomplicated relapses can nevertheless be successfully treated at the office of a family physician – mostly with steroids. Steroids are not appropriate for long-term treatment though. In those cases an early treatment with immunosuppressants in collaboration with a gastroenterologist is required. Cooperation with several different sub specialists is necessary when surgery is required as well as for the treatment of fistula, psychosomatic aspects and extraintestinal manifestations.

Leitlinie „Diagnostik und Therapie des Morbus Crohn“ – Kurzfassung für Internisten und Hausärzte@@@Clinical Practice Guideline on Diagnosis and Treatment of Crohn’s Disease – Summary for the General Practitioner

The German clinical practice guideline on diagnosis and therapy of Crohns disease is the result of an evidence-based consensus conference under the auspices of the German Gastroenterologic Society and the Competence Network IBD. This article will summarize the recommendations most important for the general practitioner.Crohns disease is diagnosed in cooperation with a gastroenterologist who is performing endoscopy and possibly ultrasound. Uncomplicated relapses can nevertheless be successfully treated at the office of a family physician - mostly with steroids. Steroids are not appropriate for long-term treatment though. In those cases an early treatment with immunosuppressants in collaboration with a gastroenterologist is required. Cooperation with several different sub specialists is necessary when surgery is required as well as for the treatment of fistula, psychosomatic aspects and extraintestinal manifestations.ZusammenfassungDie Leitlinie „Diagnostik und Therapie des Morbus Crohn“ ist das Ergebnis einer evidenzbasierten Konsensuskonferenz, die von der Deutschen Gesellschaft für Verdauungs- und Stoffwechselkrankheiten zusammen mit dem Kompetenznetz Chronisch entzündliche Darmerkrankungen ausgerichtet wurde. Hier sollen die für die praktische Arbeit von Internisten und Hausärzten wesentlichen Empfehlungen zusammengetragen werden.Während die initiale Diagnostik wegen der apparativen Untersuchungen die Zusammenarbeit mit einem endoskopierenden Kollegen erfordert, kann der unkomplizierte Schub in der hausärzlichen Praxis zumeist mit Steroiden erfolgreich behandelt werden. Für die Langzeittherapie sind Steroide aber ungeeignet. Hier sollte rechtzeitig eine Therapie mit Immunsuppressiva in Zusammenarbeit mit einem Gastroenterologen erfolgen. Bei notwendigen Operationen, der Therapie von Fisteln, psychosomatischen Aspekten und extraintestinalen Manifestationen ist die Zusammenarbeit mit Fachärzten verschiedener anderer Disziplinen notwendig.AbstractThe German clinical practice guideline on diagnosis and therapy of Crohn’s disease is the result of an evidence-based consensus conference under the auspices of the German Gastroenterologic Society and the Competence Network IBD. This article will summarize the recommendations most important for the general practitioner.Crohn’s disease is diagnosed in cooperation with a gastroenterologist who is performing endoscopy and possibly ultrasound. Uncomplicated relapses can nevertheless be successfully treated at the office of a family physician – mostly with steroids. Steroids are not appropriate for long-term treatment though. In those cases an early treatment with immunosuppressants in collaboration with a gastroenterologist is required. Cooperation with several different sub specialists is necessary when surgery is required as well as for the treatment of fistula, psychosomatic aspects and extraintestinal manifestations.