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Irritable bowel syndrome (IBS) is a common chronic gastrointestinal disorder of unknown pathological origin that is associated with psychological distress and reduced health‐related quality of life (HRQoL). We investigated the effects of stress‐management for adults with IBS on typical symptoms, HRQoL and mental health. With predefined criteria (patients: adults with IBS; intervention: stress‐management; control: care as usual or waitlist; outcome: patient‐relevant; study‐type: controlled trials), we registered the study with PROSPERO (168030) and searched the main medical databases. Two researchers independently reviewed the publications and assessed the risk of bias using the Scottish Intercollegiate Guidelines Network checklist. We performed meta‐analysis with homogeneous trials of acceptable quality. After screening 6656 publications, ten suitable randomized trials of acceptable (n = 5) or low methodological quality (n = 5) involving 587 patients were identified. Our meta‐analysis showed no effect of stress‐management on IBS severity 1–2 months after the intervention (Hedges' g = −0.23, 95%‐CI = −0.84 to −0.38, I2 = 86.1%), and after 3–12 months (Hedges' g = −0.77, 95%‐CI = −1.77 to −0.23, I2 = 93.3%). One trial found a short‐term reduction of symptoms, and one trial found symptom relief in the long‐term (at 6 months). One of two studies that examined HRQoL found an improvement (after 2 months). One of two studies that examined depression and anxiety found a reduction of these symptoms (after 3 weeks). Stress‐management may be beneficial for patients with IBS regarding the short‐term reduction of bowel and mental health symptoms, whereas long‐term benefits are unclear. Good quality RCTs with more than 6 months follow‐up are needed. [ABSTRACT FROM AUTHOR]

Importantly, B-cell values in children after resolution of cGvHD were not different from the non-cGvHD control group, which is strikingly different from adult cGvHD-patients, in which B-cell numbers remain depressed at least for two years after alloSCT (Glauzy I et al i , [4]). This indicates that bone marrow B-lymphopoiesis is less affected by cGvHD in children, which is in accordance with observations that children exhibit more bone marrow B-cell precursors after chemotherapy and alloSCT (Bras I et al i , [2]) and more signal joint kappa-deleting recombination excision circles (sjKRECs) (Nakatani I et al i , [8]) in the regenerative phase compared to adults. We extend these findings by showing that the distribution of bone marrow B-cell subsets as well as absolute peripheral B-cell counts exhibit no major alterations neither before nor during cGvHD. In summary, our analysis of T- and B-cell reconstitution reveals a preserved naïve CD4 SP + sp T-cell regeneration and a more robust B-cell regeneration during and after cGvHD in children compared to what is known from adult cGvHD patients. [Extracted from the article]

We demonstrate in this paper that CDK4 which is a G1 phase specific cell cycle regulator and catalytic subunit of D-type cyclins has oncogenic activity similar to D-type cyclins themselves and is able to provoke focus formation when cotransfected with activated Ha-ras into primary rat embryo fibroblasts. Surprisingly, using two different mutants we show that CDK4's ability to bind to p16INK4a and not its kinase activity is important for its transforming potential. In addition, p16INK4a but not a mutant form that is found in human tumours can completely abrogate focus formation by CDK4 suggesting that CDK4 can malignantly transform cells by sequestering p16INK4a or other CKIs. We demonstrate that both cyclin D1 and CDK4 functionally depend on active Myc to exert their potential as oncogenes and vice versa that the transforming ability of Myc requires functional cyclin D/CDK complexes. Moreover, we find that p16INK4a and the Rb related protein p107 which releases Myc after phosphorylation by cyclin D1/CDK4 efficiently block Myc's activity as a transcriptional transactivator and as an oncogene. We conclude that both p16INK4a and cyclin D/CDK4 complexes are upstream regulators of Myc and directly govern Myc function in transcriptional transactivation and transformation via the pocket protein p107. [ABSTRACT FROM AUTHOR]

Background: People with complex symptomatology but unclear diagnosis presenting to a centre for rare diseases (CRD) may present with mental (co-)morbidity. We hypothesised that combining an expert in somatic medicine with a mental health specialist working in tandem will improve the diagnostic outcome., Methods: Patients aged 12 years and older who presented to one of the 11 participating German CRDs with an unknown diagnosis were recruited into this prospective cohort trial with a two-phase cohort design. From October 1, 2018 to September 30, 2019, participants were allocated to standard care (SC, N = 684), and from October 1, 2019 to January 31, 2021 to innovative care (IC, N = 695). The cohorts consisted mainly of adult participants with only a minority of children included (N = 67). IC included the involvement of a mental health specialist in all aspects of care (e.g., assessing medical records, clinic visits, telehealth care, and case conferences). Clinicaltrials.gov identifier: NCT03563677., Findings: The proportion of patients with diagnoses established within 12 months after the first visit to the CRD explaining the entire symptomatology (primary outcome) was 19% (N = 131 of 672) in the SC and 42% (N = 286 of 686) in the IC cohort (OR adjusted for centre effects 3.45 [95% CrI: 1.99-5.65]). The difference was mainly due to a higher prevalence of mental disorders and non-rare somatic diseases in the IC cohort. The median time to explaining diagnoses was one month shorter with IC (95% CrI: 1-2), and significantly more patients could be referred to local regular care in the IC (27.5%; N = 181 of 659) compared to the SC (12.3%; N = 81 of 658) cohort (OR adjusted for centre effects 2.70 [95% CrI: 2.02-3.60]). At 12-month follow-up, patient satisfaction with care was significantly higher in the IC compared to the SC cohort, while quality of life was not different between cohorts., Interpretation: Our findings suggested that including a mental health specialist in the entire evaluation process of CRDs for undiagnosed adolescents and adults should become an integral part of the assessment of individuals with a suspected rare disease., Funding: The study was funded by the Global Innovation Fund from the Joint Federal Committee in Germany (Innovationsfonds des Gemeinsamen Bundesausschusses), grant number 01NVF17031., Competing Interests: HH, MB and TM report funding from the Bavarian State Ministry of Science and the Arts paid to their institution to support projects on rare diseases unrelated to ZSE-DUO. HH also reports unrelated funding to his institution by the Federal Ministry of Education and Research, and honoraria from Springer Verlag, Takeda Pharma GmbH and Chiesi GmbH. JD reports funding to his institution from the German Research Association, German Secretary of Education and Research, and the Innovation Fund for several unrelated projects. GH's institution has received funding from the Innovation Fund for another project. OT's institution has received funding from the European Regional Development Fund, EU Horizon 2020, Leibniz Association, and the Federal Ministry of Education and Research. OT has received royalties as an author. CZ reports funding to her institution by the Federal Ministry of Education and Research and the European Union, and voluntary work for the advisory board of the severe chronic neutropenia international registry. All other authors declare no competing interests., (© 2023 The Author(s).)

Irritable bowel syndrome (IBS) is a common chronic gastrointestinal disorder of unknown pathological origin that is associated with psychological distress and reduced health-related quality of life (HRQoL). We investigated the effects of stress-management for adults with IBS on typical symptoms, HRQoL and mental health. With predefined criteria (patients: adults with IBS; intervention: stress-management; control: care as usual or waitlist; outcome: patient-relevant; study-type: controlled trials), we registered the study with PROSPERO (168030) and searched the main medical databases. Two researchers independently reviewed the publications and assessed the risk of bias using the Scottish Intercollegiate Guidelines Network checklist. We performed meta-analysis with homogeneous trials of acceptable quality. After screening 6656 publications, ten suitable randomized trials of acceptable (n = 5) or low methodological quality (n = 5) involving 587 patients were identified. Our meta-analysis showed no effect of stress-management on IBS severity 1-2 months after the intervention (Hedges' g = -0.23, 95%-CI = -0.84 to -0.38, I 2  = 86.1%), and after 3-12 months (Hedges' g = -0.77, 95%-CI = -1.77 to -0.23, I 2  = 93.3%). One trial found a short-term reduction of symptoms, and one trial found symptom relief in the long-term (at 6 months). One of two studies that examined HRQoL found an improvement (after 2 months). One of two studies that examined depression and anxiety found a reduction of these symptoms (after 3 weeks). Stress-management may be beneficial for patients with IBS regarding the short-term reduction of bowel and mental health symptoms, whereas long-term benefits are unclear. Good quality RCTs with more than 6 months follow-up are needed., (© 2023 The Authors. Stress and Health published by John Wiley & Sons Ltd.)

Complexity of outpatient intensive care for ventilated people: Cross-mapping into the standardised NNN-taxonomy Abstract. Background: In Germany, free text is the preferred method for recording the nursing process in outpatient intensive care, although classification systems could enable a more precise description. Research question: How is nursing care for people with outpatient ventilation represented by the NNN-taxonomy and what are the recommendations for nursing practice? Methods: A qualitative "multiple case" design was applied. Using deductive content analysis (data sources: nursing documentation and secondary analysis of interviews with affected persons), several cases, both individually and across all cases were linked to the NNN-taxonomy (cross-mapping). Results: In total, the nursing documentation of 16 invasively ventilated persons with a mean age of 58.4 years ( SD = 16.3) was analysed. Seven persons additionally contributed interview data. Documentation was mainly based on the "Strukturmodell" (14/16) with a moderate to high accuracy (D-Catch Score: 16.6; SD = 4.1). Cross-mapping resulted in 4016 codes: 618 nursing diagnoses, 1956 interventions and 1442 outcomes. Documentation was strongly measure-oriented, not very person-centred and with a lack of differentiation between diagnosis and intervention. Conclusions: To improve nursing practice, a person-centred attitude and the ability to differentiate between nursing diagnoses, interventions and outcomes should be promoted.

Background: Outpatient intensive care for people with long-term mechanical ventilation is a rapidly growing area with a wide range of care demands. The aim of this Scoping Review is to present the current state of research on the quality of care for people with home mechanical ventilation in Germany and to identify research gaps., Methods: Based on predefined inclusion criteria, 4 databases were searched for publications dealing with the care of people with home ventilation in Germany. The method of "data driven thematic analysis" led the data extraction and analysis. Distinction was made between research and expert opinion., Results: The search resulted in 493 matches of which 68 publications were included in the this study: two guidelines (3%), 45 (66%) research papers and 21 (31%) expert opinions. The following topics were identified: Organization and control of ventilation (n=43; 63%), nursing (n=23; 34%), medical (n=39; 57%), therapeutic (n=7; 10%) and assistive technologies care (n=24; 35%), as well as the perspective of people with home mechanical ventilation and their relatives (n=33; 49%) and other topics (n=13; 19%)., Conclusion: Although the debate on the quality of care for people living with home mechanical ventilation is conducted broadly, studies focusing on individual care demands, autonomy and participation depending on the living situation or on the role of specific health professionals within the interprofessional team are missing., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenskonflikt besteht. Peter Heuschmann berichtet neben den Zuwendungen des Gemeinsamen Bundesausschusses (G-BA) im Rahmen des Innovationsfonds (welcher im Artikel als offizieller Förderer der Studie genannt ist) über weitere Zuwendungen außerhalb der Studie: – Bundesministerium für Forschung und Bildung– Deutsche Forschungsgemeinschaft– Europäische Union– Charité – Universitätsmedizin Berlin – Ärztekammer Berlin– Deutsche Parkinson-Gesellschaft– Universitätsklinikum Würzburg– Robert-Koch-Institut– Deutsche Herzstiftung– Gemeinsamer Bundesausschuss (G-BA) im Rahmen des Innovationsfonds– Universitätsklinikum Heidelberg (im Rahmen von RASUNOA-prime; gefördert durch ein unbefristetes Forschungsstipendium an das Universitätsklinikum Heidelberg von Bayer, BMS, Boehringer-Ingelheim, Daiichi Sankyo)– Charité – Universitätsmedizin Berlin (innerhalb Mondafis; gefördert durch ein unbefristetes Forschungsstipendium an die Charité von Bayer)– Universität Göttingen (innerhalb FIND-AF randomisiert; gefördert durch ein unbefristetes Forschungsstipendium an die Universität Göttingen von Boehringer-Ingelheim), (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

In Germany various concepts for treating patients with Parkinson's disease (PD) are available, e.g. oral medication with levodopa or deep brain stimulation (DBS), depending on the stage and severity of symptoms and also multidisciplinary management up to intersectoral treatment approaches (e.g. complex PD treatment and integrative care concepts). Nevertheless, in the treatment of patients with PD a comprehensive provision of services and a nationwide standardized collation of treatment quality are so far lacking. This is particularly true for technically complicated procedures, which necessitate a high standard of expertise by the treating physician. Some of these challenges could be overcome by expanding digital approaches (e.g. teleneurological consultation and wearables) and by introducing quality assurance initiatives (e.g. comprehensive registries and certification programs).

Background and Purpose: To evaluate the frequency and outcome of haemorrhagic transformation (HT) after ischaemic stroke in patients treated with non-vitamin K antagonist oral anticoagulants (NOACs)., Methods: Patients with stroke on treatment with a NOAC were prospectively enrolled in this multicentre observational study between February 2012 and 2015. Brain imaging at admission and follow-up imaging until day 7 were reviewed for HT. Functional outcome was assessed by the modified Rankin scale (mRS) before the index event, at discharge, and at 3-months., Results: 231 patients without recanalisation therapy (no-RT), and 32 patients with RT were eligible for analysis. Any HT was present at admission in 9/231 no-RT patients (3.9%, 95% CI 2.0 to 7.3) and in none of the patients with RT. In patients with follow-up imaging (no-RT, n=129, and RT, n=32), HT was present in 14.0% (no-RT; 95% CI, 8.9 to 21.1), and 40.6% (RT, 95% CI, 25.5 to 57.8), respectively. After adjustment for stroke severity, this difference between the no-RT and RT groups became non-significant. Symptomatic ICH was observed in 1 patient per group. HT was not associated with unfavourable outcome (mRS 3-6) at 3-months in multivariable analysis. Resumption of OAC after stroke was delayed in patients with HT compared to those without (15 d [IQR, 5-26] vs. 1 d [0-4], P <0.001)., Conclusions: The frequency and severity of HT after stroke on NOAC appears similar to previous reports for vitamin K antagonists and no anticoagulation. Whether asymptomatic HT should delay resumption of preventive anticoagulation requires further investigation., Competing Interests: The authors have no financial conflicts of interest.

Aim: The goal was to analyze the link between blood levels of calcidiol and all-cause, cardiac and infectious diseases, and mortality due to cancer in hemodialysis patients., Patients and Methods: This study retrospectively evaluated a representative sub-cohort (n=6,518) of German hemodialysis patients from the incidence cohorts 1997-2006., Results: Most (58.8%) were found to be vitamin D deficient (25(OH)D<20 ng/ml), with 41.2% being severely deficient (25(OH)D<12.5 ng/ml). All-cause mortality risk more than doubled in patients with severe deficiency (adjusted odds ratio (aOR)=2.67; 95% confidence interval (CI)=2.30-3.10; p<0.0001). Comparable data were obtained for mortality from cardiac disease (aOR=1.57; 95% CI=1.30-1.88; p<0.0001), infectious disease (aOR=1.48; 95% CI=1.15-1.90; p=0.0026), and cancer (aOR=1.51; 95% CI=1.09-2.08; p=0.0121), respectively., Conclusion: These data highlight the need to ensure primarily adequate 25(OH)D levels in dialysis patients for an advantage of survival.