RepoMed (Medizinische Hochschule Hannover)
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Lentiviral genetic barcoding for functional characterization of human umbilical cord derived mesenchymal stromal cells
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Generation of three induced pluripotent stem cell lines (MHHi012-A, MHHi013-A, MHHi014-A) from a family with Loeys-Dietz syndrome carrying a heterozygous p.M253I (c.759G>A) mutation in the TGFBR1 gene.
No full textLoeys-Dietz syndrome (LDS) is a rare connective tissue disorder characterized by a genetic predisposition for thoracic aortic aneurysm and dissection. Despite heterozygous loss-of-function mutations in genes for ligand, receptor, or downstream mediators of the transforming growth factor β (TGFβ) pathway, LDS is associated with a signature of high TGFβ signaling. We generated induced pluripotent stem cell (iPSC) lines from three adult LDS-patients (two male, one female) of a family with a heterozygous point mutation in exon 4 of the TGFβ-receptor1 (TGFBR1) gene (p.M253I; c.759G>A). The lines offer a valuable resource for modeling the pathophysiology of genetically mediated aortic disease
A rare case of a traumatic posterior hip dislocation in a 3-year-old boy: a case report and review of the literature
No full textWe present a rare case of neglected hip dislocation in a 3-year-old boy. Hip dislocations in childhood represent less than 6% of all injuries. The boy presented to the ED with ongoing hip pain after his leg got stuck in a carousel. The physical and radiologic examination revealed a posterior right hip dislocation. The closed reduction failed, so open reduction during surgery was performed. The postoperative protocol included 3 days of immobilization with early mobilization and pain-adapted weight bearing. No signs of femoral head malperfusion occurred 2 months after the injury. The patient did not complain of any limitations such as weight bearing problems or loss of range of motion. In comparison to adults, there are several specialties such as the fact that minor trauma can lead to hip dislocations due to the laxity of the ligaments, and due to the limited direct anamnestic options, neglected hip dislocations can occur. The treatment should focus on immediate proper reduction. The main complications after traumatic hip dislocation are avascular necrosis of the femoral head, redislocation, and early osteoarthritis
Public preferences for the allocation of donor organs for transplantation: Focus group discussions.
No full textBACKGROUND:Deceased donor organs are scarce resources because of a large supply-and-demand mismatch. This scarcity leads to an ethical dilemma, forcing priority-setting of how these organs should be allocated and whom to leave behind. OBJECTIVE:To explore public preferences for the allocation of donor organs in regard to ethical aspects of distributive justice. METHODS:Focus groups were facilitated between November and December 2018 at Hannover Medical School. Participants were recruited locally. Transcripts were assessed with content analysis using the deductive framework method. All identified and discussed criteria were grouped according to the principles of distributive justice and reported following the COREQ statement. RESULTS:Six focus groups with 31 participants were conducted. Overall, no group made a final decision of how to allocate donor organ; however, we observed that not only a single criterion/principle but rather a combination of criteria/principles is relevant. Therefore, the public wants to allocate organs to save as many lives as possible by both maximizing success for and also giving priority to urgent patients considering the best compatibility. Age, waiting time, reciprocity and healthy lifestyles should be used as additional criteria, while sex, financial status and family responsibility should not, based on aspects of equality. CONCLUSIONS:All participants recognized the dilemma that prioritizing one patient might cause another one to die. They discussed mainly the unclear trade-offs between effectiveness/benefit and medical urgency and did not establish an agreement about their importance. The results suggest a need of preference studies to elucidate public preferences in organ allocation
Incidence, risk factors and healthcare costs of central line-associated nosocomial bloodstream infections in hematologic and oncologic patients.
No full textNon-implanted central vascular catheters (CVC) are frequently required for therapy in hospitalized patients with hematological malignancies or solid tumors. However, CVCs may represent a source for bloodstream infections (central line-associated bloodstream infections, CLABSI) and, thus, may increase morbidity and mortality of these patients. A retrospective cohort study over 3 years was performed. Risk factors were determined and evaluated by a multivariable logistic regression analysis. Healthcare costs of CLABSI were analyzed in a matched case-control study. In total 610 patients got included with a CLABSI incidence of 10.6 cases per 1,000 CVC days. The use of more than one CVC per case, CVC insertion for conditioning for stem cell transplantation, acute myeloid leukemia, leukocytopenia (≤ 1000/μL), carbapenem therapy and pulmonary diseases were independent risk factors for CLABSI. Hospital costs directly attributed to the onset of CLABSI were 8,810 € per case. CLABSI had a significant impact on the overall healthcare costs. Knowledge about risk factors and infection control measures for CLABSI prevention is crucial for best clinical practice
Identification of a rare SEPT9 variant in a family with autosomal dominant Charcot-Marie-Tooth disease
No full textBackground: Charcot-Marie-Tooth disease (CMT) is one of the most commonly inherited neurological disorders. A growing number of genes, involved in glial and neuronal functions, have been associated with different subtypes of CMT leading to improved diagnostics and understanding of pathophysiological mechanisms. However, some patients and families remain genetically unsolved. Methods: We report on a German family including four affected members over three generations with a CMT phenotype accompanied by cognitive deficits, predominantly with regard to visual abilities and episodic memory. Results: A comprehensive clinical characterization followed by a sequential diagnostic approach disclosed a heterozygous rare SEPT9 missense variant c.1406 T > C, p.(Val469Ala), that segregates with disease. SEPT9 has been linked to various intracellular functions, such as cytokinesis and membrane trafficking. Interestingly, SEPT9-mutations are known to cause hereditary neuralgic amyotrophy (HNA), a recurrent focal peripheral neuropathy. Conclusion: We, for the first time, present a SEPT9 variant associated to a CMT phenotype and suggest SEPT9 as new sufficient candidate gene in CMT
miR-21-KO Alleviates Alveolar Structural Remodeling and Inflammatory Signaling in Acute Lung Injury.
No full textAcute lung injury (ALI) is characterized by enhanced permeability of the air-blood barrier, pulmonary edema, and hypoxemia. MicroRNA-21 (miR-21) was shown to be involved in pulmonary remodeling and the pathology of ALI, and we hypothesized that miR-21 knock-out (KO) reduces injury and remodeling in ALI. ALI was induced in miR-21 KO and C57BL/6N (wildtype, WT) mice by an intranasal administration of 75 µg lipopolysaccharide (LPS) in saline (n = 10 per group). The control mice received saline alone (n = 7 per group). After 24 h, lung function was measured. The lungs were then excised for proteomics, cytokine, and stereological analysis to address inflammatory signaling and structural damage. LPS exposure induced ALI in both strains, however, only WT mice showed increased tissue resistance and septal thickening upon LPS treatment. Septal alterations due to LPS exposure in WT mice consisted of an increase in extracellular matrix (ECM), including collagen fibrils, elastic fibers, and amorphous ECM. Proteomics analysis revealed that the inflammatory response was dampened in miR-21 KO mice with reduced platelet and neutrophil activation compared with WT mice. The WT mice showed more functional and structural changes and inflammatory signaling in ALI than miR-21 KO mice, confirming the hypothesis that miR-21 KO reduces the development of pathological changes in ALI
Comparison of exclusion, imputation and modelling of missing binary outcome data in frequentist network meta-analysis
Get PDFDNA Methylation of the t-PA Gene Differs Between Various Immune Cell Subtypes Isolated From Depressed Patients Receiving Electroconvulsive Therapy.
Get PDFBackground:Major depressive disorder (MDD) represents a tremendous health threat to the world's population. Electroconvulsive therapy (ECT) is the most effective treatment option for refractory MDD patients. Ample evidence suggests brain-derived neurotrophic factor (BDNF) to play a crucial role in ECT's mode of action. Tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) are involved in BDNF production. Hypothesis:The DNA methylation of gene regions encoding for t-PA and PAI-1 might be a suitable biomarker for ECT response prediction. Methods:We withdrew blood from two cohorts of treatment-resistant MDD patients receiving ECT. In the first cohort (n = 59), blood was collected at baseline only. To evaluate DNA methylation changes throughout the treatment course, we acquired a second group (n = 28) and took blood samples at multiple time points. DNA isolated from whole blood and defined immune cell subtypes (B cells, monocytes, natural killer cells, and T cells) served for epigenetic analyses. Results:Mixed linear models (corrected for multiple testing by Sidak's post-hoc test) revealed (1) no detectable baseline blood DNA methylation differences between ECT remitters (n = 33) and non-remitters (n = 53) in the regions analyzed, but (2) a significant difference in t-PA's DNA methylation between the investigated immune cell subtypes instead (p < 0.00001). This difference remained stable throughout the treatment course, showed no acute changes after ECT, and was independent of clinical remission. Conclusion:DNA methylation of both proteins seems to play a minor role in ECT's mechanisms. Generally, we recommend using defined immune cell subtypes (instead of whole blood only) for DNA methylation analyses