RepoMed (Medizinische Hochschule Hannover)
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Reduced humoral but stable cellular SARS-CoV-2-specific immunity in liver transplant recipients in the first year after COVID-19.
Get PDFMortality due to COVID-19 is not increased in immunosuppressed individuals after liver transplantation (OLT) compared to individuals without immunosuppression. Data on long-term protective immunity against SARS-CoV-2 in immunosuppressed convalescents, is limited. We prospectively measured immune responses against SARS-CoV-2 by quantifying antibodies against 4 different antigens (spike protein 1 and 2, receptor binding domain, nucleocapsid) and T cell responses by IFN-γ ELISPOT against 4 antigens (membrane, nucleocapsid, spike protein 1 and 2) in 24 OLT convalescents with immunosuppressive therapy longitudinally in the first year after COVID-19 including a booster vaccination in comparison to a matched cohort of non-immunosuppressed convalescents (non-IS-Con). Pre-pandemic OLT samples were retrieved from our prospective OLT biorepository (n = 16). No relevant T cell reactivity or immunoglobulin G (IgG) against SARS-CoV-2 were detectable in pre-pandemic samples of OLT recipients despite reactivity against endemic corona-viruses. OLT convalescents had a lower prevalence of IgG against nucleocapsid (54% vs. 90%) but not against spike protein domains (98-100% vs. 100%) after vaccination in the second half-year after COVID-19 compared to non-IS-Con. Also, concentrations of anti-nucleocapsid IgG were lower in OLT convalescents than in non-IS-Con. Concentration of IgG against spike protein domains was significantly increased by a booster vaccination in OLT convalescents. But concentration of IgG against two of three spike protein domains remains slightly lower compared to non-IS-Con finally. However, none of these differences was mirrored by the cellular immunity against SARS-CoV-2 that remained stable during the first year after COVID-19 and was not further stimulated by a corona vaccination in OLT convalescents. In conclusion, despite lower concentrations of anti-SARS-CoV-2 IgG in OLT convalescents anti-SARS-CoV-2 cellular immunity was as robust as in non-IS-Con
Evaluation of tissue shrinkage after CT-guided microwave ablation in patients with liver malignancies using Jacobian determinant
No full textPurpose To assess short-term tissue shrinkage in patients with liver malignancies undergoing computed tomography (CT)-guided microwave ablation (MWA) using Jacobian determinant (JD). Materials and methods Twenty-nine patients with 29 hepatic malignancies (primary n = 24; metastases n = 5; median tumor diameter 18 mm) referred to CT-guided MWA (single position; 10 min, 100 W) were included in this retrospective IRB-approved study, after exclusion of five patients. Following segmentation of livers and tumors on pre-interventional images, segmentations were registered on post-interventional images. JD mapping was applied to quantify voxelwise tissue volume changes after MWA. Percentual volume changes were evaluated in the ablated tumor, a 5-cm tumor perimeter and in the whole liver and compared in different clinical conditions (tumor entity: primary vs. secondary; tumor location: subcapsular vs. non-subcapsular; tumor volume: >/6ml, compared with smaller tumors, in which tissue expansion was noted (median -1.0 vs. 2.5%; p = 0.002). Other clinical conditions had no significant influence on the extent of tissue shrinkage (p > 0.05). Conclusion 3D Jacobian analysis shows that hepatic tissue deformation following MWA is most pronounced in a 5-cm area surrounding the treated tumor. Tumor location and tumor volume may have an impact on the extent of tissue shrinkage which may affect estimation of the safety margin
Identifizierung der metastasierungsabhängigen CpG-Insel-Methylierung von NHLH2 beim humanen Nierenzellkarzinom und Assoziation mit dem progressionsfreien Überleben
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Cell-Free Hemoglobin in Acute Kidney Injury after Lung Transplantation and Experimental Renal Ischemia/Reperfusion.
Get PDFCell-free hemoglobin (CFH), a pro-oxidant and cytotoxic compound that is released in hemolysis, has been associated with nephrotoxicity. Lung transplantation (LuTx) is a clinical condition with a high incidence of acute kidney injury (AKI). In this study, we investigated the plasma levels of CFH and haptoglobin, a CFH-binding serum protein, in prospectively enrolled LuTx patients (n = 20) with and without AKI. LuTx patients with postoperative AKI had higher CFH plasma levels at the end of surgery compared with no-AKI patients, and CFH correlated with serum creatinine at 48 h. Moreover, CFH levels inversely correlated with haptoglobin levels, which were significantly reduced at the end of surgery in LuTx patients with AKI. Because multiple other factors can contribute to AKI development in the complex clinical setting of LuTx, we next investigated the role of exogenous CFH administration in a mouse model of mild bilateral renal ischemia reperfusion injury (IRI). Exogenous administration of CFH after reperfusion caused overt AKI with creatinine increase, tubular injury, and enhanced markers of renal inflammation compared with vehicle-treated animals. In conclusion, CFH is a possible factor contributing to postoperative AKI after LuTx and promotes AKI in an experimental model of mild transient renal ischemia. Targeting CFH might be a therapeutic option to prevent AKI after LuTx
Profit Analysis of Minimal-invasive Approaches for Surgical Treatment of A3 Spinal Burst Fractures
Get PDFBackground/aim Regarding the surgical treatment of incomplete burst fractures of the spine, no optimal standard procedure has been established. While previous studies have focused on radiological and surgical outcome parameters, the literature has not elucidated economic aspects of various surgical treatment options in detail yet. This study aimed to investigate whether open and minimal-invasive approaches differ in their economic profit gain. Furthermore, we examined whether a single-stage or two-stage approach of anterior-posterior fusion was more profitable. Patients and methods By analyzing retrospectively data of 129 patients who underwent surgical procedure due to isolated incomplete burst fractures, we examined the economic profit and radiological parameter of open pedicle screw insertion, minimal-invasive techniques (percutaneous screws, percutaneous screws combined with SpineJack®, kyphoplasty or SpineJack®), and anterior-posterior fusion. Results Percutaneous screws in combination with SpineJack® gained significantly higher profit and higher profit per day of hospital length of stay. Profit was similar after single-stage and two-stage approach of vertebral body replacement. No significant difference in radiological outcome after 24 months was detected between the various surgical techniques. Conclusion From a financial aspect, our finding suggests that application of percutaneous screws in combination with SpineJack® may generate the highest economic profit gain regarding treatment of incomplete burst fracture
<<Fit for School>> - development and evaluation of a structured diabetes education course for 5- to 7-year-old children to support save start in primary school
No full textBackground: The feasibility of structured diabetes education for preschool-aged children has not yet been evaluated. A multiprofessional team developed a structured 2-day diabetes training tailored to the cognitive developmental level of 5- to 7-year-old children. Objective: To assess the acceptability of the structured education and its impact on quality of life, social inclusion, and glycemic control during the first six months of school attendance. Methods: At study entry and at six-month follow-up, parents of participating children answered questionnaires on their child's health-related quality of life (Kiddy-Kindl), self-management skills, glycemic control, and satisfaction with the program. Results: Overall 88 children (mean (SD) age: 6.4 (0.4) years; diabetes duration: 2.8 (1.6) years; 56% boys, 97% insulin pump) participated in the education course; at study entry all parents answered the questionnaire, 80% at follow-up. Parents evaluated their child’s health-related quality of life higher compared to parents of children in the general population (mean (SD) Kiddy-Kindl total score: 84.71 (7.4) vs. 80.04 (8.1); P < 0.001). In school all children participated in exercise lessons and one-day trips. Parents of 77% of the children reported that diabetes did not interfere with their child’s school performance. Children's median HbA1c remained stable over six months at 7.3% [55.3 mmol/mol], P = 0.624). All parents recommended the course to other families with preschool children with diabetes. Conclusion: The diabetes training for preschoolers is feasible und may contribute to a successful start in school with social inclusion, high quality of life, and stable glycemic control. Die Daten wurden durch die Autorinnen persönlich während der Patientenschulungen am Kinderkrankenhaus AUF DER BULT Hannover erhoben und doppelt in die Datenbank eingegeben und überprüft. Die somatischen Parameter wurden im Rahmen der ambulanten Langzeitbetreuung der Kinder mit T1D erhoben, die Einschätzungen der Eltern wurden mit evaluierten psychometrischen Messinstrumenten erhoben. The study procedures were approved by the Ethical Committee on Human Studies at Hannover Medical School (no. 7979_BO_K_2017) in accordance with the Declaration of Helsinki
General practitioners' willingness to participate in research networks in Germany.
No full textObjectives To investigate general practitioners' (GPs') willingness to participate in long-term medical research and in research networks (RNs). Design and setting Cross-sectional survey among German GPs around Halle-Wittenberg and Leipzig in 2020. Subjects Random sample of 905 GPs. Main outcome measures and results Response rate 37%, 69% female. Overall, 57% were interested in participating in medical research, 34% in an active role in a RN. Interest in RN participation was positively associated with male sex, younger age, previous experiences in medical research, being involved in teaching undergraduates, and having qualification in a further specialty. Main motivators were improving patient care, giving a more realistic picture of GP care, and carrying out research on topics within their own interest areas and a reliable contact person at the leading institution. Most GPs were not afraid of reduced earnings; however, time investment was the main barrier for participation. GPs were willing to dedicate twice as much time to research when remuneration was offered. High rated topics were polypharmacy, chronic diseases, drug safety and adverse drug reactions. Conclusion GPs are interested to participate in practice-based research. The study results providing useful and generalizable insights in barriers and motivators should be considered when building and running GP-RNs.KEY POINTSThere is a difference between general practitioners' (GPs') overall interest in clinical research and their job and socio-demographic related readiness to participate in research networks (RNs).GPs are interested in RNs when it is a resource of and leading to enhanced patient-oriented care.GPs are willing to dedicate twice as much time to research when remunerated.GPs need a reliable counterpart within the leading institution
Lyz2-Cre-Mediated Genetic Deletion of Septin7 Reveals a Role of Septins in Macrophage Cytokinesis and Kras-Driven Tumorigenesis
No full textBy crossing septin7-floxed mice with Lyz2-Cre mice carrying the Cre recombinase inserted in the Lysozyme-M (Lyz2) gene locus we aimed the specific deletion of septin7 in myeloid cells, such as monocytes, macrophages and granulocytes. Septin7 flox/flox :Lyz2-Cre mice show no alterations in the myeloid compartment. Septin7-deleted macrophages (BMDMs) were isolated and analyzed. The lack of Septin7 expression was confirmed and a constitutive double-nucleation was detected in Septin7-deficient BMDMs indicating a defect in macrophage cytokinesis. However, phagocytic function of macrophages as judged by uptake of labelled E. coli particles and LPS-stimulated macrophage activation as judged by induction of TNF mRNA expression and TNF secretion were not compromised. In addition to myeloid cells, Lyz2-Cre is also active in type II pneumocytes (AT2 cells). We monitored lung adenocarcinoma formation in these mice by crossing them with the conditional knock-in Kras-LSL-G12D allele. Interestingly, we found that control mice without septin7 depletion die after 3-5 weeks, while the Septin7-deficient animals survived 11 weeks or even longer. Control mice sacrificed in the age of 4 weeks display a bronchiolo-alveolar hyperplasia with multiple adenomas, whereas the Septin7-deficient animals of the same age are normal or show only a weak multifocal brochiolo-alveolar hyperplasia. Our findings indicate an essential role of Septin7 in macrophage cytokinesis but not in macrophage function. Furthermore, septin7 seems absolutely essential for oncogenic Kras-driven lung tumorigenesis making it a potential target for anti-tumor interventions
