RepoMed (Medizinische Hochschule Hannover)
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Eine retrospektive monozentrische Analyse des Patientenaufkommens im Notfallbetrieb in der Ambulanz einer universitären Mund-, Kiefer- und Gesichtschirurgie während der ersten Kontaktbeschränkungen aufgrund der SARS-CoV-2-Pandemie
Get PDFUntersuchen der periostalen Gewebereaktion nach operativen Eingriffen unter begleitender Bisphosphonat-Therapie mittels eines Piezopräparierinstrumentes
Get PDFMolecular control of urothelial differentiation in the mouse: functional analysis of the transcription factor DNP63
Get PDFEinflussfaktoren der Wachstumsmuster bei Kindern und Jugendlichen mit Mukopolysaccharidose Typ I nach hämatopoetischer Stammzelltransplantation
Get PDFMucopolysaccharidosis type I (MPS I) is an autosomal-recessive metabolic disorder caused by an enzyme deficiency of lysosomal alpha-L-iduronidase (IDUA). Haematopoietic stem cell transplantation (HSCT) is the therapeutic option of choice in MPS I patients younger than 2.5 years, which has a positive impact on neurocognitive development. However, impaired growth remains a problem. In this monocentric study, 14 patients with MPS I (mean age 1.72 years, range 0.81–3.08) were monitored according to a standardised follow-up program after successful allogeneic HSCT. A detailed anthropometric program was carried out to identify growth patterns and to determine predictors of growth in these children. All patients are alive and in outpatient care (mean follow-up 8.1 years, range 0.1–16.0). Progressively lower standard deviation scores (SDS) were observed for body length (mean SDS !1.61; !4.58 – 3.29), weight (!0.56; !3.19 – 2.95), sitting height (!3.28; !7.37 – 0.26), leg length (!1.64; !3.88 – 1.49) and head circumference (0.91; !2.52 – 6.09). Already at the age of 24 months, significant disproportions were detected being associated with increasing deterioration in growth for age. Younger age at HSCT, lower counts for haemoglobin and platelets, lower potassium, higher donor-derived chimerism, higher counts for leukocytes and recruitment of a matched unrelated donor (MUD) positively correlated with body length (p ! 0.05). In conclusion, this study characterised predictors and aspects of growth patterns in children with MPS I after HSCT, underlining that early HSCT of MUD is essential for slowing body disproportion
Development of an in vitro genotoxicity assay to detect retroviral vector-induced lymphoid insertional mutants
Get PDFSafety assessment in retroviral vector-mediated gene therapy remains challenging. In clinical trials for different blood and immune disorders, insertional mutagenesis led to myeloid and lymphoid leukemia. We previously developed the In Vitro Immortalization Assay (IVIM) and Surrogate Assay for Genotoxicity Assessment (SAGA) for pre-clinical genotoxicity prediction of integrating vectors. Murine hematopoietic stem and progenitor cells (mHSPCs) transduced with mutagenic vectors acquire a proliferation advantage under limiting dilution (IVIM) and activate stem cell- and cancer-related transcriptional programs (SAGA). However, both assays present an intrinsic myeloid bias due to culture conditions. To detect lymphoid mutants, we differentiated mHSPCs to mature T cells and analyzed their phenotype, insertion site pattern, and gene expression changes after transduction with retroviral vectors. Mutagenic vectors induced a block in differentiation at an early progenitor stage (double-negative 2) compared to fully differentiated untransduced mock cultures. Arrested samples harbored high-risk insertions close to Lmo2, frequently observed in clinical trials with severe adverse events. Lymphoid insertional mutants displayed a unique gene expression signature identified by SAGA. The gene expression-based highly sensitive molecular readout will broaden our understanding of vector-induced oncogenicity and help in pre-clinical prediction of retroviral genotoxicity
Predicting overt hepatic encephalopathy after TIPS: value of three minimal hepatic encephalopathy tests
Get PDFBackground & aims Hepatic encephalopathy (HE) is a frequent and severe complication in patients after transjugular intrahepatic portosystemic shunt (TIPS) insertion. However, risk factors for post-TIPS HE remain poorly defined. Minimal HE (mHE) is a well-known risk factor for overt HE in patients with cirrhosis without TIPS. We aimed to evaluate three tools frequently used for diagnosing mHE for their dynamic changes and their predictive value for overt HE after TIPS. Methods We prospectively recruited 84 consecutive patients before TIPS insertion and monitored them for 180 days for post-TIPS HE. Before TIPS insertion, the patients underwent the portosystemic encephalopathy (PSE) syndrome test, the animal naming test (ANT), and the critical flicker frequency (CFF). Patients were retested after TIPS insertion. Results The majority of patients were male (67.9%), and the predominant indication for TIPS was refractory ascites (75%). Median age was 59 years, model for end-stage liver disease score was 12, and 66.3%, 64.6%, and 28.4% patients had evidence for mHE according to the PSE syndrome test, ANT, and CFF, respectively. Overall, 25 patients developed post-TIPS HE within 180 days after TIPS insertion. Post-TIPS incidence of overt HE was 22.2, 28.6, 45.5, and 55.6% in those with no, one, two, and three pathological tests at baseline, respectively. However, none of the three tests was significantly associated with post-TIPS HE. Of note, mean performance in all tests remained stable over time after TIPS insertion. Conclusions PSE syndrome test, ANT and CFF, which are frequently used for diagnosing mHE have limited value for predicting HE after TIPS insertion. We could not find evidence that TIPS insertion leads to a psychometric decline in the long term. Impact and implications This prospective observational study compared three diagnostic tests for mHE and showed the limited value of these tests for predicting overt HE in patients with cirrhosis undergoing TIPS insertion. In addition, the results suggest that cognitive performance generally remains stable after TIPS insertion. These results are important for physicians and researchers involved in the management of patients with cirrhosis undergoing TIPS procedures. The study's findings serve as a starting point for further investigations on the development of more effective strategies for predicting and managing post-TIPS HE. Clinical trial number ClinicalTrials.gov NCT04801290
Optimal treatment of the underlying aetiology is the most effective antimicrobial stewardship for chronic respiratory disease: a lesson learned from cystic fibrosis
Get PDFInvestigating the clinical benefit of circulating long non-coding RNAs to improve the specificity of high-sensitive Troponin T in patients with ACS
Get PDFTensions between the Professions: How Integrated Care Can Benefit from Better Understanding and Managing Conflicting Perspectives and Demands.
Get PDFIn the transition from fragmented to integrated care, tensions are inevitable. Contradictions between the actors of the different professions involved can have negative but also positive effects on change processes in the healthcare system. This is especially true for integrated care, where collaboration among the workforce is pivotal. Therefore, efforts should not be made to avoid tensions from the outset, if this is at all possible, but to deal with them constructively. The attention of leading actors must be increased to recognize, analyse, and successfully manage tensions. The creative potential of tensions can be harnessed to successfully implement integrated care and engage the diverse workforce
Post-approval studies with the CFTR modulators Elexacaftor-Tezacaftor-Ivacaftor
Get PDFTriple combination therapy with the CFTR modulators elexacaftor (ELX), tezacaftor (TEZ) and ivacaftor (IVA) has been qualified as a game changer in cystic fibrosis (CF). We provide an overview of the body of literature on ELX/TEZ/IVA published between November 2019 and February 2023 after approval by the regulators. Recombinant ELX/TEZ/IVA-bound Phe508del CFTR exhibits a wild type conformation in vitro, but in patient's tissue a CFTR glyoisoform is synthesized that is distinct from the wild type and Phe508del isoforms. ELX/TEZ/IVA therapy improved the quality of life of people with CF in the real-life setting irrespective of their anthropometry and lung function at baseline. ELX/TEZ/IVA improved sinonasal and abdominal disease, lung function and morphology, airway microbiology and the basic defect of impaired epithelial chloride and bicarbonate transport. Pregnancy rates were increasing in women with CF. Side effects of mental status changes deserve particular attention in the future