RepoMed (Medizinische Hochschule Hannover)
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MicroRNA Profiles of Maternal and Neonatal Endothelial Progenitor Cells in Preeclampsia.
No full textPreeclampsia is associated with an increased cardiovascular morbidity of mother and offspring, thus contributing to a substantial burden in women and children's health. It has been proven that endothelial progenitor cell (EPC) numbers and functional characteristics are impaired in cardiovascular disease and preeclampsia, although causative factors for the latter have remained elusive. MicroRNA (miRNA) modifications are a potential mechanism through which exposure to an altered environment translates into the development of chronic disease. In this study, we examined whether development of preeclampsia corresponds to alterations of miRNAs in maternal- and cord-blood-derived EPC. To test this end, we analyzed maternal and neonatal miRNAs via RNA sequencing from endothelial cells of preeclamptic and healthy controls in different cell culture passages. We were able to demonstrate differentially represented miRNAs in all groups. Hsa-miR-1270 showed significantly different levels in cord blood EPC from preeclampsia versus control and was negatively correlated with mRNA levels of its predicted targets ANGPTL7 and TFRC. Transfection with an hsa-miR-1270 inhibitor decreased the tube formation capacity and chemotactic motility but did not change proliferation in vitro. Target predictions and gene set enrichment analyses identified alternative splicing as a significantly enriched pathway for hsa-miR-1270. The top miRNAs in three other groups were predicted to target transcriptional and developmental pathways. Here, we showed for the first time significantly different levels of miRNAs and differently represented mRNA levels of predicted target genes in EPC derived from preeclampsia. Understanding the effects of preeclampsia on the epigenetic mechanisms of EPC will be crucial and may provide initial insights for further evaluation of the benefits of therapies targeting this cell population
Pharmacokinetics of Meropenem in People with Cystic Fibrosis: a Proof of Concept Clinical Trial
No full textAnti-infective treatment of pulmonary exacerbations is a major issue in people with cystic fibrosis (CF). Individualized dosing strategies and adaptation of infusion times are important concepts to optimize anti-infective therapy. In this prospective non-randomized controlled open-label trial, we compared pharmacokinetics of meropenem in 12 people with CF experiencing a pulmonary exacerbation, of whom six received parenteral meropenem 2 g tid as short infusion over 30 min and six extended infusion over 120 min. We measured blood concentrations of meropenem at five predetermined time points over 240 min and calculated differences in the percentages of the time above the minimal inhibitory concentration (fT > MIC) for meropenem concentrations >16 and >32 mg/L, respectively. Mean percentages of fT > 16 and fT > 32 mg/L were higher in the extended compared to the short infusion group (83 and 56% vs. 59% and 34%), with a statistically significant prolongation of the fT > 32 mg/L (mean 134 vs. 82 min; p = 0.037). Our results demonstrate that, in people with CF, longer fT > MIC can be achieved with a simple modification of meropenem dosing. Further studies are needed to clarify if this may translate into improved microbiological and clinical outcomes, in particular in adults with difficult-to-treat chronic infection by carbapenem-resistant Pseudomonas aeruginosa
The Inverse Spacer: a Novel, Safe, and Cost-Effective Approach in Routine Procedures for Revision Knee Arthroplasty
No full textBackground A major disadvantage of current spacers for two-stage revision total knee arthroplasty (R-TKA) is the risk of (sub-) luxation during mobilization in the prosthesis-free interval, limiting their clinical success with detrimental consequences for the patient. The present study introduces a novel inverse spacer, which prevents major complications, such as spacer (sub-) luxations and/or fractures of spacer or bone. Methods The hand-made inverse spacer consisted of convex tibial and concave femoral components of polymethylmethacrylate bone cement and was intra-operatively molded under maximum longitudinal tension in 5° flexion and 5° valgus position. Both components were equipped with a stem for rotational stability. This spacer was implanted during an R-TKA in 110 knees with diagnosed or suspected periprosthetic infection. Postoperative therapy included a straight leg brace and physiotherapist-guided, crutch-supported mobilization with full sole contact. X-rays were taken before and after prosthesis removal and re-implantation. Results None of the patients experienced (sub-) luxations/fractures of the spacer, periprosthetic fractures, or soft tissue compromise requiring reoperation. All patients were successfully re-implanted after a prosthesis-free interval of 8 weeks, except for three patients requiring an early exchange of the spacer due to persisting infection. In these cases, the prosthetic-free interval was prolonged for one week. Conclusion The inverse spacer in conjunction with our routine procedure is a safe and cost-effective alternative to other articulating or static spacers, and allows crutch-supported sole contact mobilization without major post-operative complications. Maximum longitudinal intra-operative tension in 5° flexion and 5° valgus position appears crucial for the success of surgery
Medium- and long-term clinical benefits of periodontal regenerative/reconstructive procedures in intrabony defects: Systematic review and network meta-analysis of randomized controlled clinical studies.
No full textBackground Systematic reviews have established the short-term improvements of periodontal regenerative/reconstructive procedures compared to conventional surgical treatment in intrabony defects. However, a hierarchy of periodontal regenerative/reconstructive procedures regarding the medium- to long-term results of treatment does not exist. Aim To systematically assess the literature to answer the focused question "In periodontitis patients with intrabony defects, what are the medium- and long-term benefits of periodontal regenerative/reconstructive procedures compared with open flap debridement (OFD), in terms of clinical and/or radiographic outcome parameters and tooth retention?". Material & methods Randomized controlled clinical trials (RCTs), reporting on clinical and/or radiographic outcome parameters of periodontal regenerative/reconstructive procedures ≥3 years post-operatively, were systematically assessed. Clinical [residual probing pocket depth (PD) and clinical attachment level (CAL) gain, tooth loss] and radiographic [residual defect depth (RDD), bone gain (RBL)] outcome parameters were assessed. Descriptive statistics were calculated, and Bayesian random-effects network meta-analyses (NMA) were performed where possible. Results Thirty RCTs, presenting data 3 to 20 years after treatment with grafting, GTR, EMD, as monotherapies, combinations thereof, and/or adjunctive use of blood-derived growth factor constructs or with OFD only, were included. NMA based on 21 RCTs showed that OFD was clearly the least efficacious treatment; regenerative/reconstructive treatments resulted in significantly shallower residual PD in 4 out 8 comparisons [range of mean differences (MD): -2.37 to -0.60 mm] and larger CAL gain in 6 out 8 comparisons (range of MD: 1.26 to 2.66 mm), and combination approaches appeared as the most efficacious. Tooth loss after regenerative/reconstructive treatment was less frequent (0.4%) compared to OFD (2.8%), but the evidence was sparse. There were only sparse radiographic data not allowing any relevant comparisons. Conclusion Periodontal regenerative/reconstructive therapy in intrabony defects results, in general, in shallower residual PD and larger CAL gain compared with OFD, translating in high rates of tooth survival, on a medium (3-5 years) to long-term basis (5-20 years). Combination approaches appear, in general, more efficacious compared to monotherapy in terms of shallower residual PD and larger CAL gain. A clear hierarchy could, however, not be established due to limited evidence
Quantifying the robustness of primary analysis results: A case study on missing outcome data in pairwise and network meta-analysis.
Get PDFConducting sensitivity analyses is an integral part of the systematic review process to explore the robustness of results derived from the primary analysis. When the primary analysis results can be sensitive to assumptions concerning a model's parameters (e.g., missingness mechanism to be missing at random), sensitivity analyses become necessary. However, what can be concluded from sensitivity analyses is not always clear. For instance, in a pairwise meta-analysis (PMA) and network meta-analysis (NMA), conducting sensitivity analyses usually boils down to examining how 'similar' the estimated treatment effects are from different re-analyses to the primary analysis or placing undue emphasis on the statistical significance. To establish objective decision rules regarding the robustness of the primary analysis results, we propose an intuitive index, which uses the whole distribution of the estimated treatment effects under the primary and alternative re-analyses. This novel index is compared to an objective threshold to infer the presence or lack of robustness. In the case of missing outcome data, we additionally propose a graph that contrasts the primary analysis results to those of alternative scenarios about the missingness mechanism in the compared arms. When robustness is questioned according to the proposed index, the suggested graph can demystify the scenarios responsible for producing inconsistent results to the primary analysis. The proposed decision framework is immediately applicable to a broad set of sensitivity analyses in PMA and NMA. We illustrate our framework in the context of missing outcome data in both PMA and NMA using published systematic reviews
A Retrospective Analysis of the Initial Effect of COVID-19 on German Prehospital Care During Lockdown in Germany.
Get PDFIntroduction This retrospective cohort analysis examines the impact of the COVID-19 pandemic in the prehospital setting in Germany. The data of two emergency physician response units of a northern German region with 1.2 million citizens was analyzed retrospectively. Materials and methods We analyzed the period March 16 to April 16 for the year 2020 when the lockdown took place in Germany and compare the results for the same period for the year 2019 and 2018. 1004 patients were included. Demographic data, the type of rescue missions, the number of missions per day, the National Advisory Committee for Aeronautics Score (NACA-score), the frequency of respiratory emergencies (COVID-19 and non-COVID-19 associated), as well as the number of deaths were documented. Results Mean age was 62.3±24.8 years and 576 (56.5%) were male. Number of missions were 397, 403 and 333 in 2018, 2019 and 2020 respectively. The control room registered a 22% reduction of rescue missions for the year 2020. Even the amount of emergency calls via the emergency number 112 was reduced by 17.4% between 2018 and 2020. 150 (14.9%) missions were due to respiratory emergencies. In 2020 10 missions (28.6% of respiratory emergencies) were COVID-19 related. In 2020 the NACA score increased significantly. Conclusion We found a decreasing effect of the COVID-19 pandemic in Germany on the number of emergency calls as well as missions, and an increase of the severity of cases in preclinical care for a northern German region with 1.2 million citizens. The effect of these findings caused by COVID-19 on the health care system remains to be seen
Newsletter der Klinik für Plastische, Ästhetische, Hand- und Wiederherstellungschirurgie - 02. Ausgabe/Juni 2021
Get PDFHebammenstudierende verkaufen keine Schuhe! Ein Kommentar zur Hebammenausbildung in Deutschland.
No full textDieser Beitrag ist ein Kommentar zur Hebammenausbildung in Deutschland aus der Perspektive einer Studiengangleitung. Er war ein Beitrag fürs VFWG-Symposium «Sind duale Studiengänge der Hebammen ein Modell für die Therapieberufe?» vom 18. März 2021.This article is a comment on midwifery education in Germany from the perspective of a program director. It was a contribution to the VFWG symposium «Are dual degree programs in midwifery a model for the therapy professions?» held on March 18, 2021
