[Clinical use of botulinum toxin type A in pain medicine]. / Klinische Anwendung von Botulinumtoxin Typ A in der Schmerzmedizin.

Botulinum toxin has been used for decades in the treatment of a variety of painful diseases. Botulinum toxin not only blocks neuromuscular transmission, but also the secretion of neuropeptides, such as substance P, glutamate and calcitonin gene-related peptide (CGRP) and thus inhibits neurogenic inflammation. In addition, it has a modulatory pain-relieving effect via retrograde transport into the central nervous system. In addition to approval for the treatment of dystonia or spasticity, onabotulinum toxin A is also approved for the prophylaxis of chronic migraine if the oral prophylactic migraine medication has had an insufficient effect or has not been tolerated. In addition, botulinum toxin is also recommended in guidelines as a third-line treatment for neuropathic pain, but in Germany this is an off-label application. This article provides an overview of the current clinically relevant areas of application of botulinum toxin in the field of pain medicine.

Histologically validated scoring system for the assessment of hock burn in broilers.

The assessment of bird-based welfare indicators plays an important role in the evaluation of bird welfare. The aim of the study was to histologically validate a visual scoring system for hock burn in broilers and to detect threshold values of a visual score to define welfare-relevant alterations in terms of mild lesions or ulcers of the hock. We collected 200 hocks of 39- to 42-day-old Ross 308 broilers after the slaughter process. Each hock was scored visually ("macro scores" 0-4) and evaluated histologically ("micro scores" 0-3), with high scores representing more severe lesions. Although we found a tendency for higher micro scores with increasing macro scores, an exact allocation of macro to micro scores was not possible. For example, macro score 1 could represent micro scores 1, 2 and 3, whereas macro scores 3 and 4 always represented micro score 3 (ulcer). The conditional probability of certain micro scores for given macro scores was estimated using a multinomial logistic regression model. Ulcer showed the highest probability at macro score 1, whereas mild lesions were not found to have an estimated highest probability at any macro score. The depth of inflammation of hock burn lesions increased with increasing macro scores up to macro score 3 with an average depth of 1019 µm. Visually more severe and deeper lesions were also histologically rated with higher scores. Thus, considering limitations, the herein validated macroscopic assessment scheme for hock burn allows an estimation of histological alterations in hocks of broilers.RESEARCH HIGHLIGHTS Histological validation of a visual assessment scheme for hock burn in broilers.Tendency for higher micro scores with increasing macro scores.Estimation of histological score via macro score possible with limitations.Histological depth of inflammation increased with an increasing macro score.

Opioid intake prior to admission is not increased in elderly patients with low-energy fractures: A case-control study in a German hospital population.

BACKGROUND: Recent studies revealed an increased prescription rate of opioids for elderly patients suffering bone fractures. To gain further insight, we conducted face-to-face interviews in the present study to compare the opioid intake between patients with low-energy fractures and patients suffering from internal diseases. METHODS: In this case-control study, 992 patients, aged 60 years and older, were enrolled between March 2014 and February 2015. The interview comprised a fall and medication history, comorbidities, mobility and other risk factors for fractures. Odds ratios (OR) and a multiple logistic regression model were calculated. RESULTS: The number of patients with pre-admission opioid intake in the last 12 months was comparable in the fracture (n = 399, 13.3%) and the control group (n = 593, 14.7% OR: 0.89, CI: 0.62-1.29). The number of patients with current opioid intake of short duration (<3 months) was similar in both groups (14% vs. 20%; OR: 0.66, CI: 0.23-1.93). Patients with opioid intake in the fracture group reported more frequently fatigue as an adverse event of opioid medication (58% vs. 30%; OR: 3.32, CI: 1.48-7.45). Patients with opioid intake showed more severe comorbidities and significantly decreased mobility compared to those without opioids. CONCLUSION: Elderly patients internalized due to low-energy fractures did not take opioids more frequently than patients with internal admission, for both short (<3 months) and longer duration intake. Patients with opioid intake were generally in poorer physical condition. The risk of fracture might increase in patients suffering from fatigue as a side effect of opioid medication. SIGNIFICANCE: This study is based on face-to-face interviews with patients, including details about side effects and fracture history, providing a more pronounced picture of the relation of opioid intake and risk of fracture.

Development of a prognostic tool for the occurrence of feather pecking and cannibalism in laying hens.

In July 2015, a German voluntary decree stipulated that the keeping of beak-trimmed laying hens after the 1st of January 2017 will no longer be permitted. Simultaneously, the present project was initiated to validate a newly developed prognostic tool for laying hen farmers to forecast, at the beginning of a laying period, the probability of future problems with feather pecking and cannibalism in their flock. For this purpose, we used a computer-based prognostic tool in form of a questionnaire that was easy and quick to complete and facilitated comparisons of different flocks. It contained various possible risk factors that were classified into 3 score categories (1 = "no need for action," 2 = "intermediate need for action," 3 = "instant need for action"). For the validation of this tool, 43 flocks of 41 farms were examined twice, at the beginning of the laying period (around the 20th wk of life) and around the 67th wk of life. At both visits, the designated investigators filled out the questionnaire and assessed the plumage condition and the skin lesions (as indicators of occurrence of feather pecking and cannibalism) of 50 laying hens of each flock. The average prognostic score of the first visit was compared with the existence of feather pecking and cannibalism in each flock at the end of the laying period. The results showed that the prognostic score was negatively correlated with the plumage score (r = -0.32; 95% confidence interval [CI]: [-0.56; -0.02]) and positively correlated with the skin lesion score (r = 0.38; 95% CI: [0.09; 0.61]). These relationships demonstrate that a better prognostic score was associated with a better plumage and skin lesion score. After performing a principal component analysis on the single scores, we found that only 6 components are sufficient to obtain highly sensitive and specific prognostic results. Thus, the data of this analysis should be used for creating applicable software for use on laying hen farms.

A four-gene LincRNA expression signature predicts risk in multiple cohorts of acute myeloid leukemia patients.

Prognostic gene expression signatures have been proposed as clinical tools to clarify therapeutic options in acute myeloid leukemia (AML). However, these signatures rely on measuring large numbers of genes and often perform poorly when applied to independent cohorts or those with older patients. Long intergenic non-coding RNAs (lincRNAs) are emerging as important regulators of cell identity and oncogenesis, but knowledge of their utility as prognostic markers in AML is limited. Here we analyze transcriptomic data from multiple cohorts of clinically annotated AML patients and report that (i) microarrays designed for coding gene expression can be repurposed to yield robust lincRNA expression data, (ii) some lincRNA genes are located in close proximity to hematopoietic coding genes and show strong expression correlations in AML, (iii) lincRNA gene expression patterns distinguish cytogenetic and molecular subtypes of AML, (iv) lincRNA signatures composed of three or four genes are independent predictors of clinical outcome and further dichotomize survival in European Leukemia Net (ELN) risk groups and (v) an analytical tool based on logistic regression analysis of quantitative PCR measurement of four lincRNA genes (LINC4) can be used to determine risk in AML.

Evaluation of welfare parameters in laying hens on the basis of a Bavarian survey.

Health issues like infestation with poultry red mite (Dermanyssus gallinae) and behavioral problems such as feather pecking and cannibalism are reported as current problems on laying hen farms. However, the epidemiological prevalence of these issues in Bavaria, Germany, is not known. The objective of the present survey was to determine the epidemiological prevalence of health and behavioral parameters and the management of hen farms in practice. The survey was sent to all laying hen farmers with more than 1,000 hens in Bavaria, Germany, and contained questions regarding flock management, behavior problems and health issues. The response rate was 40.8% and surveys were answered regarding 293 individual flocks on 147 farms. Three-quarters (77.6%) of the respondents housed their hens under conventional conditions. Farming system had an influence (P ≤ 0.05) on several management measures and the hens' behavior. An infestation of the flocks with poultry red mite was stated in 65.7%, whereby a relationship existed with the farming system (P = 0.001) and the provision of an additional dust bath (P ≤ 0.001). The occurrence of feather pecking (18.5%) was related with the farming system (P = 0.001), the presence of roosters (P = 0.034), the locking of laying hens into the aviary (P = 0.006), not allowing access to the entire litter space after housing (P = 0.044) and nervous (P = 0.002) or chasing behavior (P ≤ 0.001) of laying hens. Similarly, cannibalism (15.0%) was related with locking hens into the aviary system (P ≤ 0.001) and not allowing access to the entire litter space (P = 0.026). According to these results, farmers should avoid locking the hens into the aviary or not allowing access to the entire litter space, because these measures relate to nervous behavior that may result in feather pecking or cannibalism. The provision of an additional dust bath is one of the management measures that can positively influence hens' health and behavior.

Enantiomer-specific and paracrine leukemogenicity of mutant IDH metabolite 2-hydroxyglutarate.

Canonical mutations in IDH1 and IDH2 produce high levels of the R-enantiomer of 2-hydroxyglutarate (R-2HG), which is a competitive inhibitor of α-ketoglutarate (αKG)-dependent enzymes and a putative oncometabolite. Mutant IDH1 collaborates with HoxA9 to induce monocytic leukemia in vivo. We used two mouse models and a patient-derived acute myeloid leukemia xenotransplantation (PDX) model to evaluate the in vivo transforming potential of R-2HG, S-2HG and αKG independent of the mutant IDH1 protein. We show that R-2HG, but not S-2HG or αKG, is an oncometabolite in vivo that does not require the mutant IDH1 protein to induce hyperleukocytosis and to accelerate the onset of murine and human leukemia. Thus, circulating R-2HG acts in a paracrine manner and can drive the expansion of many different leukemic and preleukemic clones that may express wild-type IDH1, and therefore can be a driver of clonal evolution and diversity. In addition, we show that the mutant IDH1 protein is a stronger oncogene than R-2HG alone when comparable intracellular R-2HG levels are achieved. We therefore propose R-2HG-independent oncogenic functions of mutant IDH1 that may need to be targeted in addition to R-2HG production to exploit the full therapeutic potential of IDH1 inhibition.

Hyperactivation of mTORC1 and mTORC2 by multiple oncogenic events causes addiction to eIF4E-dependent mRNA translation in T-cell leukemia.

High activation of the PI3K-AKT-mTOR pathway is characteristic for T-cell acute lymphoblastic leukemia (T-ALL). The activity of the master regulator of this pathway, PTEN, is often impaired in T-ALL. However, experimental evidence suggests that input from receptor tyrosine kinases (RTKs) is required for sustained mTOR activation, even in the absence of PTEN. We previously reported the expression of Neurotrophin receptor tyrosine kinases (TRKs) and their respective ligands in primary human leukemia samples. In the present study we aimed to dissect the downstream signaling cascades of TRK-induced T-ALL in a murine model and show that T-ALLs induced by deregulated receptor tyrosine kinase signaling acquire activating mutations in Notch1 and lose PTEN during clonal evolution. Some clones additionally lost one allele of the homeodomain transcription factor Cux1. All events independently led to a gradual hyperactivation of both mTORC1 and mTORC2 signaling. We dissected the role of the individual mTOR complexes by shRNA knockdown and found that the separate depletion of mTORC1 or mTORC2 reduced the growth of T-ALL blasts, but was not sufficient to induce apoptosis. In contrast, knockdown of the mTOR downstream effector eIF4E caused a striking cytotoxic effect, demonstrating a critical addiction to cap-dependent mRNA-translation. Although high mTORC2-AKT activation is commonly associated with drug-resistance, we demonstrate that T-ALL displaying a strong mTORC2-AKT activation were specifically susceptible to 4EGI-1, an inhibitor of the eIF4E-eIF4G interaction. To decipher the mechanism of 4EGI-1, we performed a genome-wide analysis of mRNAs that are translationally regulated by 4EGI-1 in T-ALL. 4EGI-1 effectively reduced the ribosomal occupancy of mRNAs that were strongly upregulated in T-ALL blasts compared with normal thymocytes including transcripts important for translation, mitochondria and cell cycle progression, such as cyclins and ribosomal proteins. These data suggest that disrupting the eIF4E-eIF4G interaction constitutes a promising therapy strategy in mTOR-deregulated T-cell leukemia.

Constitutive IRF8 expression inhibits AML by activation of repressed immune response signaling.

Myeloid differentiation is blocked in acute myeloid leukemia (AML), but the molecular mechanisms are not well characterized. Meningioma 1 (MN1) is overexpressed in AML patients and confers resistance to all-trans retinoic acid-induced differentiation. To understand the role of MN1 as a transcriptional regulator in myeloid differentiation, we fused transcriptional activation (VP16) or repression (M33) domains with MN1 and characterized these cells in vivo. Transcriptional activation of MN1 target genes induced myeloproliferative disease with long latency and differentiation potential to mature neutrophils. A large proportion of differentially expressed genes between leukemic MN1 and differentiation-permissive MN1VP16 cells belonged to the immune response pathway like interferon-response factor (Irf) 8 and Ccl9. As MN1 is a cofactor of MEIS1 and retinoic acid receptor alpha (RARA), we compared chromatin occupancy between these genes. Immune response genes that were upregulated in MN1VP16 cells were co-targeted by MN1 and MEIS1, but not RARA, suggesting that myeloid differentiation is blocked through transcriptional repression of shared target genes of MN1 and MEIS1. Constitutive expression of Irf8 or its target gene Ccl9 identified these genes as potent inhibitors of murine and human leukemias in vivo. Our data show that MN1 prevents activation of the immune response pathway, and suggest restoration of IRF8 signaling as therapeutic target in AML.

Repeated exclusive enteral nutrition in the treatment of paediatric Crohn's disease: predictors of efficacy and outcome.

BACKGROUND: Exclusive enteral nutrition (EEN) induces remission and mucosal healing in children with active Crohn's disease (CD). AIM: To compare short- and long-term outcomes of the first vs. second courses of EEN, and to identify predictors of sustained remission. METHODS: Retrospective single centre analysis of all patients with CD (6-18 years) treated with EEN over 7.5 years. Patients were excluded if exposed to anti-TNFα or corticosteroids 3 months prior to EEN. Data included disease phenotype, activity, NOD2 genotype, laboratory indices and anthropometrics. Remission and relapse were defined by mathematically weighted Paediatric Crohn's Disease Activity Index (wPCDAI) with 1-year follow-up. RESULTS: Of 94 patients treated with EEN, 52 fulfilled inclusion criteria (31 male, mean age 13.2 years). Azathioprine was started within the first month in 33/52 patients; 26/52 received a second EEN course. First compared to second EEN revealed higher wPCDAI at start (59 vs. 40, P < 0.0001), tended to higher remission rates after 3 months (92% vs. 77%, n.s.), but showed comparable 1-year relapse rates (67% vs. 70%, median time 231 vs. 145 days, n.s.). Disease activity, weight gain and inflammatory markers showed better improvement with first EEN. Faecal calprotectin >200 µg/g during EEN was associated with shorter remission (median time 157 vs. 287 days, n.s.). Certain NOD2 genotypes were related to higher relapse rates (92% R702W or G908R vs. 50% 1007fs vs. 60% wild-type, P < 0.01). CONCLUSIONS: Exclusive enteral nutrition induces remission in active Crohn's disease, but efficacy tends to decrease with the second course. Despite early azathioprine use, 1-year relapse rates are high, but may be related to NOD2 genotype.

[Dependency syndrome and hyperalgesia due to an opioid therapy for curative treatable pain. Case report of an apparent palliative patient]. / Abhängigkeitssyndrom und Hyperalgesie durch Opioide bei kurativ behandelbaren Schmerzen. Fallbericht zu einem scheinbaren Palliativpatienten.

Opioids are an essential part of cancer pain management but particularly in this patient group physicians could misinterpret opioid-induced potentially life-threatening side effects within the central nervous system (CNS) or hyperalgesia as a consequence of tumor progression. In this case increasing the opioid dose or switching to rapidly acting opioids may trigger a vicious circle. We describe a case report of a male patient who was treated with high doses of transdermal and endonasal fentanyl 2 years after pancreatomy due to cancer. The patient was referred to the palliative care unit presenting with delirious behavior and 30-40 severe abdominal pain attacks/day. After withdrawal of the opioid medication all CNS symptoms disappeared. Further diagnostics revealed multiple incisional hernia as the reason of the pain syndrome. The patient recovered after herniotomy and has now been pain free without any pain medication for more than 16 months. This case report underlines again the necessity of pain diagnostics also in assumed palliative patients with the risks of high dose opioid treatment.

Activation of Evi1 inhibits cell cycle progression and differentiation of hematopoietic progenitor cells.

The transcription factor Evi1 has an outstanding role in the formation and transformation of hematopoietic cells. Its activation by chromosomal rearrangement induces a myelodysplastic syndrome with progression to acute myeloid leukemia of poor prognosis. Similarly, retroviral insertion-mediated upregulation confers a competitive advantage to transplanted hematopoietic cells, triggering clonal dominance or even leukemia. To study the molecular and functional response of primary murine hematopoietic progenitor cells to the activation of Evi1, we established an inducible lentiviral expression system. EVI1 had a biphasic effect with initial growth inhibition and retarded myeloid differentiation linked to enhanced survival of myeloblasts in long-term cultures. Gene expression microarray analysis revealed that within 24 h EVI1 upregulated 'stemness' genes characteristic for long-term hematopoietic stem cells (Aldh1a1, Abca1, Cdkn1b, Cdkn1c, Epcam, among others) but downregulated genes involved in DNA replication (Cyclins and their kinases, among others) and DNA repair (including Brca1, Brca2, Rad51). Cell cycle analysis demonstrated EVI1's anti-proliferative effect to be strictly dose-dependent with accumulation of cells in G0/G1, but preservation of a small fraction of long-term proliferating cells. Although confined to cultured cells, our study contributes to new hypotheses addressing the mechanisms and molecular targets involved in preleukemic clonal dominance or leukemic transformation by Evi1.

[Accidental levomethadone intoxication in a palliative patient]. / Akzidentielle Levomethadonintoxikation bei einer Palliativpatientin.

Levomethadone is a strong opioid which is used rarely in the treatment of special pain syndromes in Germany. A main field for the usage of Levomethadone, which has be applied as a oral fluid, is the opioid replacement therapy of heroin-addicts. Due to the long plasma half life and its high inter-individual variability, the application implies a risk of cumulation leading to an overdosage. It is not recommended to use a fixed equianalgesic formula for the dosage conversion from other opioids. The conversion starts with a low start dose, an individual titration follows. In this case-report, the difficulty of cumulation, inaccurate drug dispensary and the characteristic of dosage calculation of levomethadone is discussed.

New effective treatment regimen for children infected with a double-resistant Helicobacter pylori strain.

BACKGROUND: The increasing number of pediatric patients infected with multiresistant Helicobacter pylori strains calls for evaluation of treatment regimens. Second-line antibiotics such as tetracycline or quinolones are not licensed for children. Because in vivo resistance to metronidazole may be overcome in vivo by a high dose and prolonged intake, we evaluated the eradication rate and side effects of a high-dose triple therapy in pediatric patients with culture-proven double resistance. PATIENTS AND METHODS: In this open multicentre trial, 62 children (<18 years, body weight >15 kg) infected with an H pylori strain resistant to metronidazole and clarithromycin were treated according to body weight classes with amoxicillin (∼ 75 mg/kg/day), metronidazole (∼ 25 mg/kg/day) and esomeprazole (∼ 1.5 mg/kg/day) for 2 weeks. Adherence and adverse events were assessed by a 2-week diary and telephone interviews at days 7 and 14 of treatment. Primary outcome was a negative C-urea breath test after 6 weeks. RESULTS: Of 62 patients, 5 were lost to follow-up, 12 were nonadherent, and 45 treated per protocol. Eradication rates were 66% (41/62) [confidence interval 54-78] (intention to treat) and 73% (33/45) [confidence interval 60-86] (per protocol). Success of treatment was not related to dose per kilogram body weight. Mild to moderate adverse events were reported by 21 patients, including nausea (10.8%), diarrhoea (8.9%), vomiting (7.1%), abdominal pain (5.4%), and headache (3.6%), and led to discontinuation in 1 child. CONCLUSION: High-dose amoxicillin, metronidazole, and esomeprazole for 2 weeks is a good treatment option in children infected with a double resistant H pylori strain.

Delayed gastric emptying in patients with Prader Willi Syndrome.

BACKGROUND: A 15 year old girl with Prader-Willi Syndrome (PWS) died of gastric rupture. Systematic literature research revealed seven case reports of PWS patients with acute gastric dilatation, two had a lethal course. The objective of this study was to determine if delayed gastric emptying in PWS patients might contribute to gastric dilatation. METHODS: Gastric emptying was measured in eight patients with PWS by nucleotid scintigraphy after a standardized test meal. RESULTS: Median age was 17.8 years (range 10.1-19.5). Median BMI of the male patients was 29.5 (range 18.4-34.8), of the female patients 28 (range 20.0-44.8). Half time of gastric emptying was delayed in five of the eight patients (median 78.5 minutes, range 59-134). CONCLUSION: Scintigraphic measurement of gastric emptying in eight PWS patients revealed delay in comparison to normal values. This might be a risk factor for gastric dilatation and rupture in patients with PWS.

S3-guideline "helicobacter pylori and gastroduodenal ulcer disease" of the German society for digestive and metabolic diseases (DGVS) in cooperation with the German society for hygiene and microbiology, society for pediatric gastroenterology and nutrition e. V., German society for rheumatology, AWMF-registration-no. 021 / 001.

This guideline updates a prior consensus recommendation of the German Society for Digestive and Metabolic Diseases (DGVS) from 1996. It was developed by an interdisciplinary cooperation with representatives of the German Society for Hygiene and Microbiology, the Society for Pediatric Gastroenterology and Nutrition (GPGE), and the German Society for Rheumatology. The guideline is methodologically based on recommendations of the Association of the Scientific Medical Societies in Germany (AWMF) for providing a systematic evidence-based S 3 level consensus guideline and has also implemented grading criteria according to the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) process. Clinical applicability of study results as well as specifics for Germany in terms of epidemiology, antibiotic resistance status, diagnostics, and therapy were taken into account.

Improved performance of a rapid office-based stool test for detection of Helicobacter pylori in children before and after therapy.

A modified version of a rapid office based one-step monoclonal immunoassay for detection of Helicobacter pylori antigen in stool samples from children was evaluated against biopsy specimen-based methods and compared to a monoclonal enzyme immunoassay using the same antigen. Blinded stool samples from 185 children (0.3 to 18.2 years) were investigated at the time of upper endoscopy prior to anti-H. pylori therapy; 62 children were H. pylori infected and 123 noninfected according to predefined reference standards. Samples obtained 6 to 8 weeks after anti-H. pylori therapy were available from 58 children (3.8 to 17.7 years) and were compared to results of the [(13)C]urea breath test (14/58 were positive). The rapid stool tests were performed by two independent readers. Of 243 rapid tests performed, 1 (0.4%) was invalid for technical reasons. Equivocal results (very weak line) were reported 16 times by reader 1 and 27 times by reader 2. When equivocal results were considered positive, the two observers agreed on 76 positive and 160 negative results and disagreed on 7 samples (2.9%). The sensitivity was 90.8% for reader 1 and 85.5% for reader 2, and the specificity was 91.0% and 93.4%, respectively. The monoclonal enzyme immunoassay revealed a sensitivity and specificity of 94.7% and 97.6%, respectively. The modified chromatographic immunoassay is a good alternative in settings or situations when the monoclonal enzyme immunoassay or the [(13)C]urea breath test are not available or feasible. In order to improve sensitivity, very weak lines should be considered positive test results.

[The role of next of kin in medical decision-making--empirical findings from haemato-oncological diseases]. / Die Rolle der Angehörigen bei medizinischen Entscheidungen--Empirische Befunde zu hämatoonkologischen Erkrankungen.

AIM OF THE STUDY: Models of shared decision making in the patient-doctor relationship are attracting increasing attention. A recent study focuses on the so far inadequate attention paid to the role of next of kin. It was examined in which decision areas next of kin of haematological cancer patients were included, further what support next of kin could provided and finally which factors encouraged the participation of next of kin in that process. METHODS: From 2006-2008 empirical data were collected from hemato-oncological patients undergoing treatment as well as from their families. The participating family members of patients were mailed questionnaires based on the patient sample (designation of a family member by the patient: 118/177 or 66.7%) on average half of a year following the patient's (in- or outpatient) treatment. The response rate of the participants was 67.8% (80/118). Of the respondents, 65% were spouses or partners of the patients, the average age was 53.9 years, and 66.3% were female. RESULTS: Family members think it makes sense for them to take an active part in medical decisions affecting their loved ones and a majority of them reported having participated in decision-making processes concerning a variety of issues. Being involved in their loved one's discussions with their doctors has a significant influence on this. Family members' level of education was the only clear predictor for participation in discussions with doctors that could be isolated. CONCLUSION: It is clear that family members, especially spouses and partners, consider it meaningful to participate in medical decisions affecting their loved ones, and that they want to be able to do this in the clinical context. One limitation that must be mentioned is that due to the small size of the sample and an approach that focused on initial exploration, the results should be interpreted as a point of orientation. Further studies should look in more detail at how inner family structures play a role in patient-doctor shared decision-making, as well as the concrete conditions and implications that play a role in family members' participation in this process, i.e., adherence to "doctor's orders" and possible decision-making conflicts on the part of the patient.

[S3-guideline "Helicobacter pylori and gastroduodenal ulcer disease"]. / S3-Leitlinie "Helicobacter pylori und gastroduodenale Ulkuskrankheit" der Deutschen Gesellschaft für Verdauungs- und Stoffwechselkrankheiten (DGVS).

This guideline updates a prior concensus recommendation of the German Society for Digestive and Metabolic Diseases (DGVS) from 1996. It was developed by an interdisciplinary cooperation with representatives of the German Society for Microbiology, the Society for Pediatric Gastroenterology and Nutrition (GPGE) and the German Society for Rheumatology. The guideline is methodologically based on recommendations of the Association of the Scientific Medical Societies in Germany (AWMF) for providing a systematic evidence-based consensus guideline of S 3 level and has also implemented grading criteria according to GRADE (Grading of Recommendations Assessment, Development and Evaluation). Clinical applicability of study results as well as specifics for Germany in terms of epidemiology, antibiotic resistance status, diagnostics and therapy were taken into account.