Publications by authors named "F Hildebrand"

390 Publications

Ultra-resolution Metagenomics: When Enough Is Not Enough.

Authors:
Falk Hildebrand

mSystems 2021 Aug 31:e0088121. Epub 2021 Aug 31.

Gut Microbes and Health, Quadram Institute Bioscience, Norwich, United Kingdom.

Technological advances in community sequencing have steadily increased the taxonomic resolution at which microbes can be delineated. In high-resolution metagenomics, bacterial strains can now be resolved, enhancing medical microbiology and the description of microbial evolution . In the Hildebrand lab, we are researching novel approaches to further increase the phylogenetic resolution of metagenomics. I propose that ultra-resolution metagenomics will be the next qualitative level of community sequencing, classified by the accurate resolution of ultra-rare genetic events, such as subclonal mutations present in all populations of evolving cells. This will be used to quantify evolutionary processes at ecologically relevant scales, monitor the progress of infections within a patient, and accurately track pathogens in food and infection chains. However, to develop this next metagenomic generation, we first need to understand the currently imposed limits of sequencing technologies, metagenomic strain delineation, and genome reconstructions.
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http://dx.doi.org/10.1128/mSystems.00881-21DOI Listing
August 2021

Care of Geriatric Patients with Lumbar Spine, Pelvic, and Acetabular Fractures before and after Certification as a Geriatric Trauma Center DGU: A Retrospective Cohort Study.

Medicina (Kaunas) 2021 Jul 31;57(8). Epub 2021 Jul 31.

Department of Trauma and Reconstructive Surgery, RWTH University Hospital, 52074 Aachen, Germany.

More than 750,000 fragility fractures occur in Germany every year, with an expected increase in the following years. Interdisciplinary care pathways for geriatric patients are increasingly established to improve the treatment process and outcome, but there has been only limited evaluation of their use. Objectives: This study aimed to compare patient care before and after the implementation of a geriatric trauma center (GTC) in conformity with the German Society for Trauma Surgery (DGU). We performed a retrospective single-center cohort study, including 361 patients >70 years old with lumbar spine, pelvic, and acetabular fractures, admitted between January 2012 and September 2019. Patients were divided into a usual care cohort (UC, = 137) before implementation and an ortho-geriatric care cohort (OGC, = 224) after implementation of the GTC DGU. We recorded and compared demographic data, fracture type, geriatric assessment and management, therapy, complications, and various clinical parameters, e.g., length of stay, time to surgery, hours admitted to ICU, and change in walking ability. The geriatric assessment revealed significant geriatric co-morbidities and a need for geriatric intervention in 75% of the patients. With orthogeriatric co-management, a significant increase in the detection of urological complications (UC: 25.5% vs. OGC: 37.5%; = 0.021), earlier postoperative mobilization (UC: 57.1% vs. OGC: 86.3%; < 0.001), an increased prescription of anti-osteoporotic treatment at discharge (UC: 13.1% vs. OGC: 46.8%; < 0.001), and lower rates of revision surgery (UC: 5.8% vs. OGC: 3.1%; = 0.012) could be seen. Our results emphasize the improvement in patient care and clinical outcome by implementing a GTC DGU and provide opportunities for future improvement in ortho-geriatric patient care.
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http://dx.doi.org/10.3390/medicina57080794DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8398181PMC
July 2021

The Influence of Macrophage-Activating Lipopeptide-2 in Regard to Liver-Specific Changes Within a Murine Two-Hit Model.

Inflammation 2021 Aug 16. Epub 2021 Aug 16.

Department of Orthopedic Trauma Surgery, RWTH Aachen University, Aachen, Germany.

Trauma hemorrhage (TH) and subsequent sepsis are well known to frequently result in severe organ damage. Although macrophage-activating lipopeptide-2 (MALP-2) has been described to exert beneficial effects on organ damage, and further clinical course after both isolated trauma and sepsis, little is known about the impact of MALP-2 in a clinically realistic two-hit scenario of TH and subsequent sepsis. As the liver represents a key organ for the posttraumatic immune response and development of complications, the effects of MALP-2 on the posttraumatic hepatic immunologic response and tissue damage were investigated in a murine "two-hit" model. In C57BL/6 mice, blood pressure-controlled (35 ± 5 mm Hg) TH was induced. Cecal ligation and puncture (CLP) was performed 48 h after TH. Mice were divided into two control groups (control 1, TH and laparotomy without CLP; control 2, TH and CLP) and three experimental groups (TH + CLP) treated with MALP-2 at different timepoints (ETH, end of TH; ECLP, end of CLP; 6CLP, 6 h after CLP). The observation time lasted for 168 h after induction of TH. Kupffer cells (KC) were isolated and cultured, and MPO activity was analyzed. Cell culture supernatants were taken for cytokine analysis (TNF-α, IL-6, MCP-1, GM-CSF, IL-10). Histological analysis was performed using the Hepatic Injury Severity Scoring (HISS). Statistical evaluation was carried out using SPSS (version 24.0.0; IBM, Armonk, NY, USA). MPO activity of control 1 group was lowest compared with all the other groups (p < 0.01). MPO activity of control 2 group was significantly higher than that in all experimental groups (ETH (p < 0.01), ECLP (p < 0.01), and 6CLP (p = 0.03)). Within the experimental groups, MPO activity was significantly reduced in the ETH (p = 0.04) and the ECLP (p < 0.01) groups compared with the 6CLP group. Moreover, ETH was also associated with the most pronounced reduction of cytokine expression by KC (p < 0.05). HISS revealed the largest damage in the group control 2. TH and subsequent sepsis lead to a distinct immunologic reaction in the liver with an increase of cytokine expression of KC and pronounced infiltration of granulocytes with associated severe tissue damage. MALP application decreases the hepatic immune response and liver damage, with the most pronounced effects if applied at the end of TH.
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http://dx.doi.org/10.1007/s10753-021-01534-8DOI Listing
August 2021

Plasma Spray vs. Electrochemical Deposition: Toward a Better Osteogenic Effect of Hydroxyapatite Coatings on 3D-Printed Titanium Scaffolds.

Front Bioeng Biotechnol 2021 26;9:705774. Epub 2021 Jul 26.

Department of Orthopedics, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.

Surface modification of three-dimensional (3D)-printed titanium (Ti) scaffolds with hydroxyapatite (HA) has been a research hotspot in biomedical engineering. However, unlike HA coatings on a plain surface, 3D-printed Ti scaffolds have inherent porous structures that influence the characteristics of HA coatings and osteointegration. In the present study, HA coatings were successfully fabricated on 3D-printed Ti scaffolds using plasma spray and electrochemical deposition, named plasma sprayed HA (PSHA) and electrochemically deposited HA (EDHA), respectively. Compared to EDHA scaffolds, HA coatings on PSHA scaffolds were smooth and continuous. cell studies confirmed that PSHA scaffolds have better potential to promote bone mesenchymal stem cell adhesion, proliferation, and osteogenic differentiation than EDHA scaffolds in the early and late stages. Moreover, studies showed that PSHA scaffolds were endowed with superior bone repair capacity. Although the EDHA technology is simpler and more controllable, its limitation due to the crystalline and HA structures needs to be improved in the future. Thus, we believe that plasma spray is a better choice for fabricating HA coatings on implanted scaffolds, which may become a promising method for treating bone defects.
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http://dx.doi.org/10.3389/fbioe.2021.705774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350575PMC
July 2021

Reduced pre-operative skin oxygen saturation predicts revision after open reduction and internal fixation in calcaneal fractures : A reduced pre-operative oxygen saturation as measured by laser-Doppler spectrophotometry in 8 mm depth is associated with revision surgery after open reduction and internal fixation of calcaneal fractures through an extended lateral approach.

Int Orthop 2021 Aug 6. Epub 2021 Aug 6.

Department of Orthopaedic and Trauma Surgery, Lucerne Cantonal Hospital, 6000, Luzern 16, Switzerland.

Purpose: To assess which pre-operative parameters correlate with wound revisions after an extended lateral approach to the calcaneus.

Methods: Pre-operative laser-Doppler spectrophotometry was applied in patients undergoing open reduction and internal fixation. The number of wound revisions was recorded during pos-toperative follow-up. Spearman rho analysis was used to identify factors associated with wound revision and receiver operator characteristics curves were calculated for the identified factors.

Results: Thirty-four patients (29 men, 5 women; 37 calcanei) with a mean patient age of 43 ± 14 years were analyzed. The minimal oxygen saturation value at the five measurement locations as well as the minimal value for flow correlated negatively with wound revisions (p value = 0.025 and 0.038, respectively). The area under the curve for the pre-operative minimal value of oxygen saturation was 0.841 (95%CI 0.64-1.00, p = 0.028), indicating a good accuracy as a test to predict wound revision.

Conclusion: A pre-operative oxygen saturation of at least 20.5% across five measurement points along the anticipated incision identified all patients not needing a wound revision (negative predictive value 100%). On the other hand, patients with at least one measurement below 20.5% were at risk for wound revision surgery (sensitivity 100%, specificity 48.5%). ClinicalTrials.gov NCT01264146.
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http://dx.doi.org/10.1007/s00264-021-05157-4DOI Listing
August 2021
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