Inflammatory Bowel Diseases: When Natural Friends Turn into Enemies—The Importance of CpG Motifs of Bacterial DNA in Intestinal Homeostasis and Chronic Intestinal Inflammation

From numerous studies during the last years it became evident that bacteria and bacterial constituents play a decisive role both in the maintenance of intestinal immune homeostasis as well as in the development and perpetuation of chronic intestinal inflammation. In this review we focus on the role of bacterial DNA which is a potent immunomodulatory component of the bacterial flora. Bacterial DNA has been shown to be protective against experimental colitis. In contrast bacterial DNA essentially contributes to the perpetuation of an already established chronic intestinal inflammation in a Toll-like receptor (TLR)9-dependent manner. This dichotomic action may be explained by a different activation status of essential regulators of TLR signaling like Glycogen synthase kinase 3-β (GSK3-β) depending on the pre-activation status of the intestinal immune system. In this review we suggest that regulators of TLR signaling may be interesting therapeutic targets in IBD aiming at the restoration of intestinal immune homeostasis

Nodal Disease and Survival in Oral Cancer: Is Occult Metastasis a Burden Factor Compared to Preoperatively Nodal Positive Neck?

Simple Summary Occult metastasis in oral squamous cell carcinoma patients is a feared complication. However, there are barely any existing data on survival of patients suffering from occult metastasis. This study aims to compare patients with oral squamous cell carcinoma, considering survival in occult metastases and different treatment approaches. The impact of neck involvement and occult metastasis (OM) in patients with oral squamous cell carcinoma (OSCC) favors an elective neck dissection. However, there are barely any existing data on survival for patients with OM compared with patients with positive lymph nodes detected preoperatively. This study aims to compare survival curves of patients suffering from lymph nodal metastases in a preoperatively N+ neck with those suffering from OM. In addition, clinical characteristics of the primary tumor were analyzed to predict occult nodal disease. This retrospective cohort study includes patients with an OSCC treated surgically with R0 resection with or without adjuvant chemoradiotherapy between 2010 and 2016. Minimum follow-up was 60 months. Kaplan-Meier analysis was used to compare the survival between patients with and without occult metastases and patients with N+ neck to those with occult metastases. Logistic regression was used to detect potential risk factors for occult metastases. The patient cohort consisted of 226 patients. Occult metastases occurred in 16 of 226 patients. In 53 of 226 patients, neck lymph nodes were described as suspect on CT imaging but had a pN0 neck. Higher tumor grading increased the chance of occurrence of occult metastasis 2.7-fold (OR = 2.68, 95% CI: 1.07-6.7). After 12, 24, 48 and 60 months, 82.3%, 73.8%, 69% and 67% of the N0 patients, respectively, were progression free. In the group with OM occurrence, for the same periods 66.6%, 50%, 33.3% and 33.3% of the patients, respectively, were free of disease. For the same periods, respectively, 81%, 63%, 47% and 43% of the patients in the N+ group but without OM remained disease free. The predictors for progression-free survival were a positive N status (HR = 1.44, 95% CI: 1.08-1.93) and the occurrence of OM (HR = 2.33, 95% CI: 1.17-4.64). The presence of occult metastasis could lead to decreased survival and could be a burdening factor requiring treatment escalation and a more aggressive follow-up than nodal disease detected in the preoperative diagnostic imaging

Stability of remission rates in a 3-year follow-up of naturalistic treated depressed inpatients

Background Remission is a common outcome of short-term trials and the main goal of acute and longterm treatment. The longitudinal stability of remission has rarely been investigated under naturalistic treatment conditions. Methods Naturalistic multisite follow-up study. Three-year symptomatic long-term outcome of initially hospitalized tertiary care patients (N = 784) with major depressive episodes. Remission rates as well as the switch rates between remission and non-remission were reported. Results After one, two and three years 62 %, 59 % and 69 % of the observed patients met criteria for remission. During the follow-up 88 % of all patients achieved remission. 36 % of maintained remission from discharge to 3-years, 12 % of all patients never reached remission and 52 % percent showed a fluctuating course switching from remission to non-remission and vice versa. There was considerable transition between remission and non-remission. For example, from discharge to 1 year, from 1 to 2, and from 2 to 3 years 25 %, 21 % and 11 % lost remission. Conclusion Cumulative outcome rates are encouraging. Absolute rates at predefined endpoints as well as the fluctuations between these outcomes reflect the variable and chronic nature of major depression

Galectin-3 Modulates Experimental Colitis

Background: We recently identified galectin-3 (gal-3) as a new and strong fibroblast activator produced by colonic epithelial cells. Very little is known about the influence of gal-3 in inflammatory bowel disease. We, therefore, investigated the impact of gal-3 on dextran sodium sulfate (DSS)-induced colitis in a mouse model. Methods: Colonic lamina propria fibroblasts of healthy controls were used for co-incubation studies of gal-3 with gal-1, TGF-β1, IFNγ, IL-4 and IL-10. Acute and chronic DSS colitis was induced by 3% DSS in drinking water in female Balb/c mice weighing 20-22 g. Recombinant gal-3 was expressed by the pET vector system and used for a 5-day treatment in different concentrations intraperitoneally. The distal third of the colon was used for histologic analysis. Colonic cytokine expression was determined by quantitative RT-PCR. Results: In vitro, gal-3 induced IL-8 secretion was significantly reduced by co-incubation with IL-10 (5 ng/ml) and IL-4 (10 ng/ml). Acute DSS-induced colitis was ameliorated by gal-3 treatment as indicated by increased colonic length and reduced weight loss compared to that of controls. In acute and chronic colitis, gal-3 treatment resulted in a significant suppression of colonic IL-6. Conclusion: Gal-3 significantly reduces inflammation in acute and chronic DSS colitis in mice indicating a potential role in intestinal inflammation

Comparison of a pediatric practice-based therapy and an interdisciplinary ambulatory treatment in social pediatric centers for migraine in children: a nation-wide randomized-controlled trial in Germany: \textquotedblmoma - modules on migraine activity\textquotedbl

BACKGROUND Migraine is common in childhood, peaks in adolescents and persists into adulthood in at least 40% of patients. There is need for early interventions to improve the burden of disease and, if possible, reduce chronification. The aim of the project is to compare two types of ambulatory treatment strategies regarding their effect on headache days and quality of life in 6 to 11 year old children with migraine: 1) the routine care in pediatricians' practices (intervention group A) and 2) a structured interdisciplinary multimodal intervention administered at social pediatric centers (intervention group B). METHODS The study is a nation-wide cluster-randomized study. Based on the postal codes the regions are randomly assigned to the two intervention-strategies. Children with migraine are recruited in the pediatric practices, as common outpatient-care in the German health-care system. Parents rate headache frequency, intensity and acute medication intake at a daily basis via a digital smartphone application specifically designed for the study. Migraine-related disability and quality of life are assessed every 3 months. Study duration is 9 months for every participant: 3 months of baseline at the pediatric practice (both groups); 3 months of intervention at the pediatric practice (intervention group A) or at the social pediatric center (intervention group B), respectively; 3 months of follow-up at the pediatric practice (both groups). DISCUSSION Results of the planned comparison of routine care in pediatric practices and interdisciplinary social pediatric centers will be relevant for treatment of children with migraine, both for the individual and for the health care system. TRIAL REGISTRATION The study was approved by the ethics committee at the Ludwig-Maximilians-University Munich (number 18-804) and was retrospectively registered on 27 April 2021 in the WHO approved German Clinical Trials Register (number DRKS00016698 )

Low Risk of Clostridium difficile Infections in Hospitalized Patients with Inflammatory Bowel Disease in a German Tertiary Referral Center

Introduction: Many reports, mainly from the US and Canada but also a recent report from a center in Europe, have documented the increasing impact of Clostridium difficile infections in patients with inflammatory bowel disease (IBD) during the last years. To determine the prevalence of C. difficile infections in hospitalized IBD patients in a tertiary referral center in Germany, we conducted this retrospective analysis. Methods: Data of all IBD in-patients treated due to an acute flare of their IBD at the Department of Internal Medicine I of the University of Regensburg between January 1, 2001, and June 30, 2008, were analyzed. In patients with a concomitant diagnosis of C. difficile infection, further variables such as IBD-related treatment at the time of infection or outcome were examined. Results: In total, 995 in-patients with IBD were treated in this hospital [638 patients with Crohn’s disease (CD), 357 with ulcerative colitis (UC)] during the study period. Of these, 279 patients with CD and 242 patients with UC were admitted with an acute flare and suffering from diarrhea and abdominal pain. Only 10 of those were diagnosed as having a concomitant infection with C. difficile. Six patients were female and the median age was 49 years (range: 15–80). Six patients with C. difficile infections suffered from UC and 4 patients from CD, all with previous colonic involvement. Eight patients used immunosuppressive therapies; only 2 patients were treated with antibiotics before infection. Conclusion: In contrast to recent reports from other countries, only a low percentage of hospitalized patients with acute flares of their IBD were identified as having an underlying C. difficile infection in this German tertiary referral center. However, in IBD patients with an acute flare, a concomitant C. difficile infection should be excluded, especially in patients with immunosuppressive treatment and colonic involvement of their disease. Further research is needed to evaluate if regions with different risks of C. difficile infections exist and to find out more about potential reasons for this observation

Migraine and the development of additional psychiatric and pain disorders in the transition from adolescence to adulthood

Introduction: The transition from childhood to adolescence and from adolescence to adulthood are vulnerable phases in life. In these phases, late or insufficient treatment of diseases may lead to chronification and favor development of additional disorders. In adolescents, migraine often has a highly negative impact on school performance and everyday life. The hypothesis of the present study was that adolescents with migraine have a higher risk for developing additional disorders such as psychiatric disorders or other pain syndromes in the course of the disease. Materials and methods: In this study, we analyzed health insurance data of 56,597 German adolescents at the age of 15 years in the year 2006. By using the International Classification of Diseases (ICD 10), we determined a group with migraine diagnosis in the year 2006 and a control group without any headache diagnosis in 2006. We then compared both groups regarding the development of additional disorders (based on the ICD 10) during the following 10 years (2007 to 2016). Results: Adolescents with migraine had a 2.1 fold higher risk than persons without migraine diagnosis to develop an additional affective or mood disorder, a 1.8 fold higher risk to obtain neurotic, stress-related and somatoform disorders, a 1.8 fold higher risk to subsequently suffer from behavioral syndromes, a 1.6 higher risk to get back pain and a 1.5 fold higher risk for irritable bowel syndrome during the next 10 years. Conclusion: Adolescents with migraine are at risk for developing additional disorders later. Considering and addressing the patient’s risks and potential medical and psychosocial problems might improve the long-term outcome significantly

Clinical Feature and Bowel Ultrasound in Crohn’s Disease – Does Additional Information from Magnetic Resonance Imaging Affect Therapeutic Approach and When Does Extended Diagnostic Investigation Make Sense?

Background/Aims: Some suggest MRI to be superior to ultrasound in Crohn’s disease. We analyzed how often MR enterography (MRE) following a routine ultrasound leads to a change in therapeutic decision. Material and Methods: We retrospectively evaluated 47 patients with Crohn’s disease undergoing routine ultrasound examination. Actual medical history, complete blood count, C-reactive protein (CRP), and sonographic findings were assessed independently by two specialists who retrospectively provided a therapeutic proposal. Additionally, all patients received MRE. Thereafter, the specialists had to provide a new therapeutic concept regarding all the available information. Results: Evaluation of the rectum was not successful by ultrasound, but MRE gave good results. Only 1 of 7 abscesses was identified sonographically. Three of the abscesses missed at sonography were localized in the perirectal/perianal region. MRE detected more inflamed bowel segments, but ultrasound assessment of anatomically fixed bowel parts showed good recognition by MRE. With increasing CRP values, we found more positive results of ultrasound and MRE. Therapeutic change was suggested in only 18 patients. Conclusions: Ultrasound should be performed by an experienced examiner, and a proctological examination should be added. MRE is justified in cases of discrepancy between clinical findings and the results of diagnostic ultrasound and, moreover, if Crohn’s lesions are suspected at sites proximal to the terminal or neoterminal ileum